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  <cached-name>Propiomazine H1 Antihistamine Neurological Sleep Action Pathway</cached-name>
  <cached-description>Propiomazine is an ethanolamine class H1 antihistamine used to treat insomnia and allergy symptoms such as hay fever and hives. It is also used with pyridoxine in the treatment of nausea and vomiting in pregnancy. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria.

Wakefulness is regulated by histamine in the tuberomammillary nucleus, a part of the hypothalamus. Histidine is decarboxylated into histamine in the neuron. Histamine is transported into synaptic vesicles by a monoamine transporter then released into the synapse. Normally histamine would activate the H1 histamine receptor on the post-synaptic neuron in the tuberomammillary nucleus. Propiomazine inhibits the H1 histamine receptor, preventing the depolarization of the post-synaptic neuron. This prevents the wakefulness signal from being sent to the major areas of the brain, causing sleepiness. </cached-description>
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          <name>Propiomazine H1 Antihistamine Neurological Sleep Pathway</name>
          <description>Propiomazine is an ethanolamine class H1 antihistamine used to treat insomnia and allergy symptoms such as hay fever and hives. It is also used with pyridoxine in the treatment of nausea and vomiting in pregnancy. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria.

Wakefulness is regulated by histamine in the tuberomammillary nucleus, a part of the hypothalamus. Histidine is decarboxylated into histamine in the neuron. Histamine is transported into synaptic vesicles by a monoamine transporter then released into the synapse. Normally histamine would activate the H1 histamine receptor on the post-synaptic neuron in the tuberomammillary nucleus. Propiomazine inhibits the H1 histamine receptor, preventing the depolarization of the post-synaptic neuron. This prevents the wakefulness signal from being sent to the major areas of the brain, causing sleepiness. </description>
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              <text>Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.</text>
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              <id type="integer">348284</id>
              <pubmed-id>17139284</pubmed-id>
              <text>Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. doi: 10.1038/nrd2199.</text>
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              <text>Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. doi: 10.1038/nrd2132.</text>
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              <pubmed-id> 20851648</pubmed-id>
              <text>Thakkar MM: Histamine in the regulation of wakefulness. Sleep Med Rev. 2011 Feb;15(1):65-74. doi: 10.1016/j.smrv.2010.06.004. Epub 2010 Sep 20.</text>
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              <text>Passani MB, Lin JS, Hancock A, Crochet S, Blandina P: The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders. Trends Pharmacol Sci. 2004 Dec;25(12):618-25. doi: 10.1016/j.tips.2004.10.003.</text>
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            <name>Pyridoxal 5'-phosphate</name>
            <hmdb-id>HMDB0001491</hmdb-id>
            <description>This is the active form of vitamin B6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (pyridoxamine). -- Pubchem; Pyridoxal-phosphate (PLP, pyridoxal-5'-phosphate) is a cofactor of many enzymatic reactions. It is the active form of vitamin B6 which comprises three natural organic compounds, pyridoxal, pyridoxamine and pyridoxine. -- Wikipedia.</description>
            <cas>54-47-7</cas>
            <kegg-id>C00018</kegg-id>
            <pubchem-cid>1051</pubchem-cid>
            <chebi-id>18405</chebi-id>
            <biocyc-id>PYRIDOXAL_PHOSPHATE</biocyc-id>
            <chemspider-id>1022</chemspider-id>
            <drugbank-id>DB00114</drugbank-id>
            <moldb-smiles>CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O</moldb-smiles>
            <moldb-formula>C8H10NO6P</moldb-formula>
            <moldb-inchi>InChI=1S/C8H10NO6P/c1-5-8(11)7(3-10)6(2-9-5)4-15-16(12,13)14/h2-3,11H,4H2,1H3,(H2,12,13,14)</moldb-inchi>
            <moldb-inchikey>NGVDGCNFYWLIFO-UHFFFAOYSA-N</moldb-inchikey>
            <moldb-iupac>[(4-formyl-5-hydroxy-6-methylpyridin-3-yl)methoxy]phosphonic acid</moldb-iupac>
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            <moldb-mono-mass>247.024573569</moldb-mono-mass>
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            <moldb-traditional-iupac>pyridoxal phosphate</moldb-traditional-iupac>
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            <moldb-physiological-charge type="integer">-2</moldb-physiological-charge>
            <drugbank-metabolite-id nil="true"/>
            <foodb-id>FDB021820</foodb-id>
            <synonyms>Apolon b6;Biosechs;Codecarboxylase;Coenzyme b6;Hairoxal;Hexermin-p;Hi-pyridoxin;Hiadelon;Himitan;Pal-p;Plp;Phosphopyridoxal;Phosphopyridoxal coenzyme;Pidopidon;Piodel;Pydoxal;Pyridoxal 5'-phosphate;Pyridoxal 5-phosphate;Pyridoxal p;Pyridoxal phosphate;Pyridoxal-p;Pyridoxyl phosphate;Pyromijin;Sechvitan;Vitahexin-p;Vitazechs;3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinecarboxaldehyde;3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde 5-phosphate;Phosphoric acid mono-(4-formyl-5-hydroxy-6-methyl-pyridin-3-ylmethyl) ester;Pyridoxal  5-monophosphoric acid ester;Pyridoxal 5'-(dihydrogen phosphate);Pyridoxal-5'-phosphate;Pyridoxal 5'-phosphoric acid;3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde 5-phosphoric acid;Phosphate mono-(4-formyl-5-hydroxy-6-methyl-pyridin-3-ylmethyl) ester;Pyridoxal  5-monophosphate ester;Pyridoxal 5'-(dihydrogen phosphoric acid);Pyridoxal 5-phosphoric acid;Pyridoxal phosphoric acid;Pyridoxal-5'-phosphoric acid</synonyms>
            <pwc-id>PW_C001148</pwc-id>
            <short-name>Pyr-5'P</short-name>
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            <name>L-Histidine</name>
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            <description>Histidine is an alpha-amino acid with an imidazole functional group. It is one of the 22 proteinogenic amino acids. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans and other mammals. It was initially thought that it was only essential for infants, but longer-term studies established that it is also essential for adults. Infants four to six months old require 33 mg/kg of histidine. It is not clear how adults make small amounts of histidine, and dietary sources probably account for most of the histidine in the body. Histidine is a precursor for histamine and carnosine biosynthesis. Inborn errors of histidine metabolism exist and are marked by increased histidine levels in the blood. Elevated blood histidine is accompanied by a wide range of symptoms, from mental and physical retardation to poor intellectual functioning, emotional instability, tremor, ataxia and psychosis. Histidine and other imidazole compounds have anti-oxidant, anti-inflammatory and anti-secretory properties (PMID: 9605177). The efficacy of L-histidine in protecting inflamed tissue is attributed to the capacity of the imidazole ring to scavenge reactive oxygen species (ROS) generated by cells during acute inflammatory response (PMID: 9605177). Histidine, when administered in therapeutic quantities is able to inhibit cytokines and growth factors involved in cell and tissue damage (US patent 6150392). Histidine in medical therapies has its most promising trials in rheumatoid arthritis where up to 4.5 g daily have been used effectively in severely affected patients. Arthritis patients have been found to have low serum histidine levels, apparently because of very rapid removal of histidine from their blood (PMID: 1079527). Other patients besides arthritis patients that have been found to be low in serum histidine are those with chronic renal failure. Urinary levels of histidine are reduced in pediatric patients with pneumonia. (PMID: 2084459). Asthma patients exhibit increased serum levels of histidine over normal controls (PMID: 23517038).  Serum histidine levels are lower and are negatively associated with inflammation and oxidative stress in obese women (PMID: 23361591).  Histidine supplementation has been shown to reduce insulin resistance, reduce BMI and fat mass and suppress inflammation and oxidative stress in obese women with metabolic syndrome.  Histidine appears to suppress pro-inflammatory cytokine expression, possibly via the NF-?B pathway, in adipocytes (PMID: 23361591). Low plasma concentrations of histidine are associated with protein-energy wasting, inflammation, oxidative stress, and greater mortality in chronic kidney disease patients (PMID: 18541578). Histidine may have many other possible functions because it is the precursor of the ubiquitous neurohormone-neurotransmitter histamine. Histidine increases histamine in the blood and probably in the brain. Low blood histamine with low serum histidine occurs in rheumatoid arthritis patients. Low blood histamine also occurs in some manic, schizophrenic, high copper and hyperactive groups of psychiatric patients. Histidine is a useful therapy in all patients with low histamine levels. (http://www.dcnutrition.com ).


</description>
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            <drugbank-id>DB00117</drugbank-id>
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            <description>Histamine, also known as eramin or ceplene, belongs to the class of organic compounds known as 2-arylethylamines. These are primary amines that have the general formula RCCNH2, where R is an organic group. Histamine exists as a solid, soluble (in water), and a very weakly acidic compound (based on its pKa). Histamine has been found throughout most human tissues, and has also been detected in most biofluids, including feces, saliva, urine, and blood. Within the cell, histamine is primarily located in the myelin sheath. In humans, histamine is involved in the phenbenzamine H1-antihistamine action pathway, the omeprazole action pathway, the levocetirizine H1-antihistamine action pathway, and the propiomazine H1-antihistamine action pathway. Histamine is also involved in several metabolic disorders, some of which include the thiazinamium H1-antihistamine action pathway, the metiamide action pathway, the quetiapine H1-antihistamine action pathway, and the histidinemia pathway. Outside of the human body, histamine can be found in a number of food items such as daikon radish, jicama, caraway, and japanese walnut. This makes histamine a potential biomarker for the consumption of these food products. Histamine is an amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.</description>
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            <moldb-smiles>NCCC1=CNC=N1</moldb-smiles>
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            <foodb-id>FDB012596</foodb-id>
            <synonyms>1h-imidazole-4-ethanamine;2-(1h-imidazol-4-yl)ethanamine;2-(1h-imidazol-4-yl)ethylamine;2-(1h-imidazol-5-yl)ethanamine;2-(1h-imidazol-5-yl)ethylamine;2-(4-imidazolyl)ethanamine;2-(4-imidazolyl)ethylamine;2-imidazol-4-yl-ethylamine;2-imidazol-4-ylethylamine;4-(2-aminoethyl)-1h-imidazole;4-(2-aminoethyl)imidazole;4-imidazoleethylamine;5-imidazoleethylamine;Eramin;Ergamine;Ergotidine;Free histamine;Hsm;Histamine;L-histamin base;L-histamine;Theramine;B-imidazolyl-4-ethylamine;Beta-aminoethylglyoxaline;Beta-aminoethylimidazole;Beta-aminothethylglyoxaline;Beta-imidazolyl-4-ethylamine</synonyms>
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            <name>Carbon dioxide</name>
            <hmdb-id>HMDB0001967</hmdb-id>
            <description>Carbon dioxide is a colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. Carbon dioxide is produced during respiration by all animals, fungi and microorganisms that depend on living and decaying plants for food, either directly or indirectly. It is, therefore, a major component of the carbon cycle. Additionally, carbon dioxide is used by plants during photosynthesis to make sugars which may either be consumed again in respiration or used as the raw material to produce polysaccharides such as starch and cellulose, proteins and the wide variety of other organic compounds required for plant growth and development. When inhaled at concentrations much higher than usual atmospheric levels, it can produce a sour taste in the mouth and a stinging sensation in the nose and throat. These effects result from the gas dissolving in the mucous membranes and saliva, forming a weak solution of carbonic acid. Carbon dioxide is used by the food industry, the oil industry, and the chemical industry. Carbon dioxide is used to produce carbonated soft drinks and soda water. Traditionally, the carbonation in beer and sparkling wine comes about through natural fermentation, but some manufacturers carbonate these drinks artificially.</description>
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            <moldb-inchikey>CURLTUGMZLYLDI-UHFFFAOYSA-N</moldb-inchikey>
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            <synonyms>Carbon oxide;Carbon-12 dioxide;Carbonic acid anhydride;Carbonic acid gas;Carbonic anhydride;[co2];Co2;E 290;E-290;E290;R-744</synonyms>
            <pwc-id>PW_C001316</pwc-id>
            <short-name>CO2</short-name>
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            <description>Propiomazine, an atypical antipsychotic agent, is used to treat both negative and positive symptoms of schizophrenia, acute mania with bipolar disorder, agitation, and psychotic symptoms in dementia. Future uses may include the treatment of obsessive-compulsive disorder and severe behavioral disorders in autism. Structurally and pharmacologically similar to clozapine, propiomazine binds to alpha(1), dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT2) receptors.</description>
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            <moldb-iupac>1-{10-[2-(dimethylamino)propyl]-10H-phenothiazin-2-yl}propan-1-one</moldb-iupac>
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            <synonyms>10-(2-dimethylaminopropyl)-2-propionylphenothiazine;2-propionyl-10-(2-(dimethylamino)propyl)phenothiazine;3-propionyl-10-dimethylaminoisopropylphenothiazine;Propiomazina;Propiomazinum</synonyms>
            <pwc-id>PW_C009244</pwc-id>
            <short-name>Propiom</short-name>
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            <description>Calcium is essential for the normal growth and maintenance of bones and teeth, and calcium requirements must be met throughout life. Requirements are greatest during periods of growth, such as childhood, during pregnancy and when breast-feeding. Long-term calcium deficiency can lead to osteoporosis, in which the bone deteriorates and there is an increased risk of fractures. Adults need between 1,000 and 1,300 mg of calcium in their daily diet. Calcium is essential for living organisms, particularly in cell physiology, and is the most common metal in many animals. Physiologically, it exists as an ion in the body. Calcium combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Calcium is an important component of a healthy diet. A deficit can affect bone and tooth formation, while overretention can cause kidney stones. Vitamin D is needed to absorb calcium. Dairy products, such as milk and cheese, are a well-known source of calcium. However, some individuals are allergic to dairy products and even more people, particularly those of non-European descent, are lactose-intolerant, leaving them unable to consume dairy products. Fortunately, many other good sources of calcium exist. These include: seaweeds such as kelp, wakame and hijiki; nuts and seeds (like almonds and sesame); beans; amaranth; collard greens; okra; rutabaga; broccoli; kale; and fortified products such as orange juice and soy milk. Calcium has also been found to assist in the production of lymphatic fluids.</description>
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            <moldb-inchikey>BHPQYMZQTOCNFJ-UHFFFAOYSA-N</moldb-inchikey>
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            <synonyms>Ca;Calcium element;Ca(2+);Ca2+;Calcium ion;Calcium, doubly charged positive ion</synonyms>
            <pwc-id>PW_C000353</pwc-id>
            <short-name>Ca2+</short-name>
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            <description>Catalyzes the biosynthesis of histamine from histidine.
</description>
            <hmdbp-id>HMDBP00885</hmdbp-id>
            <gene-name>HDC</gene-name>
            <locus>15q21-q22</locus>
            <drugbank-id nil="true"/>
            <genbank-id>X54297</genbank-id>
            <species-id type="integer">1</species-id>
            <ec-numbers>4.1.1.22</ec-numbers>
            <synonyms nil="true"/>
            <element-states>
              <element-state>
                <id type="integer">1311</id>
                <biological-state-id type="integer">8</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">144665</id>
                <biological-state-id type="integer">1292</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">146032</id>
                <biological-state-id type="integer">1487</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">146038</id>
                <biological-state-id type="integer">789</biological-state-id>
              </element-state>
            </element-states>
          </protein>
          <protein>
            <id type="integer">1957</id>
            <name>Synaptic vesicular amine transporter</name>
            <uniprot-id>Q05940</uniprot-id>
            <description>Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis</description>
            <hmdbp-id>HMDBP02489</hmdbp-id>
            <gene-name>SLC18A2</gene-name>
            <locus>10q25</locus>
            <drugbank-id nil="true"/>
            <genbank-id>X71354</genbank-id>
            <species-id type="integer">1</species-id>
            <ec-numbers></ec-numbers>
            <synonyms nil="true"/>
            <element-states>
              <element-state>
                <id type="integer">139697</id>
                <biological-state-id type="integer">73</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">140551</id>
                <biological-state-id type="integer">866</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">140841</id>
                <biological-state-id type="integer">870</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">141306</id>
                <biological-state-id type="integer">928</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">141347</id>
                <biological-state-id type="integer">378</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">141533</id>
                <biological-state-id type="integer">932</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">143140</id>
                <biological-state-id type="integer">1098</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">143181</id>
                <biological-state-id type="integer">1119</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">143288</id>
                <biological-state-id type="integer">1137</biological-state-id>
              </element-state>
            </element-states>
          </protein>
          <protein>
            <id type="integer">2116</id>
            <name>Histamine H1 receptor</name>
            <uniprot-id>P35367</uniprot-id>
            <description>In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system</description>
            <hmdbp-id>HMDBP02823</hmdbp-id>
            <gene-name>HRH1</gene-name>
            <locus>3p25</locus>
            <drugbank-id nil="true"/>
            <genbank-id>X76786</genbank-id>
            <species-id type="integer">1</species-id>
            <ec-numbers></ec-numbers>
            <synonyms nil="true"/>
            <element-states>
              <element-state>
                <id type="integer">67312</id>
                <biological-state-id type="integer">1</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">70009</id>
                <biological-state-id type="integer">308</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">141190</id>
                <biological-state-id type="integer">787</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">143323</id>
                <biological-state-id type="integer">965</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">143613</id>
                <biological-state-id type="integer">661</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">145621</id>
                <biological-state-id type="integer">52</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">145625</id>
                <biological-state-id type="integer">1453</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">145630</id>
                <biological-state-id type="integer">1000</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">150024</id>
                <biological-state-id type="integer">1322</biological-state-id>
              </element-state>
            </element-states>
          </protein>
          <protein>
            <id type="integer">2705</id>
            <name>Voltage-dependent calcium channel subunit alpha-2/delta-1</name>
            <uniprot-id>P54289</uniprot-id>
            <description>The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-contraction coupling</description>
            <hmdbp-id>HMDBP07484</hmdbp-id>
            <gene-name>CACNA2D1</gene-name>
            <locus>7q21-q22</locus>
            <drugbank-id nil="true"/>
            <genbank-id>CH471091</genbank-id>
            <species-id type="integer">1</species-id>
            <ec-numbers></ec-numbers>
            <synonyms nil="true"/>
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              <element-state>
                <id type="integer">141884</id>
                <biological-state-id type="integer">787</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">142774</id>
                <biological-state-id type="integer">308</biological-state-id>
              </element-state>
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                <id type="integer">143078</id>
                <biological-state-id type="integer">1033</biological-state-id>
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                <biological-state-id type="integer">1118</biological-state-id>
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                <biological-state-id type="integer">52</biological-state-id>
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                <id type="integer">145165</id>
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              </element-state>
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                <id type="integer">145193</id>
                <biological-state-id type="integer">1367</biological-state-id>
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                <id type="integer">145584</id>
                <biological-state-id type="integer">74</biological-state-id>
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                <id type="integer">145955</id>
                <biological-state-id type="integer">945</biological-state-id>
              </element-state>
            </element-states>
          </protein>
          <protein>
            <id type="integer">2706</id>
            <name>Voltage-dependent calcium channel subunit alpha-2/delta-2</name>
            <uniprot-id>Q9NY47</uniprot-id>
            <description>The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). Overexpression induces apoptosis</description>
            <hmdbp-id>HMDBP07485</hmdbp-id>
            <gene-name>CACNA2D2</gene-name>
            <locus>3p21.3</locus>
            <drugbank-id nil="true"/>
            <genbank-id>AJ251368</genbank-id>
            <species-id type="integer">1</species-id>
            <ec-numbers></ec-numbers>
            <synonyms nil="true"/>
            <element-states>
              <element-state>
                <id type="integer">940</id>
                <biological-state-id type="integer">39</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">2768</id>
                <biological-state-id type="integer">45</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">3514</id>
                <biological-state-id type="integer">14</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">3539</id>
                <biological-state-id type="integer">52</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">5095</id>
                <biological-state-id type="integer">65</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">8499</id>
                <biological-state-id type="integer">228</biological-state-id>
              </element-state>
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                <id type="integer">136132</id>
                <biological-state-id type="integer">651</biological-state-id>
              </element-state>
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                <id type="integer">139532</id>
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              </element-state>
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                <id type="integer">139707</id>
                <biological-state-id type="integer">778</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">139809</id>
                <biological-state-id type="integer">204</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">139907</id>
                <biological-state-id type="integer">48</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">140586</id>
                <biological-state-id type="integer">74</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">140624</id>
                <biological-state-id type="integer">308</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">140634</id>
                <biological-state-id type="integer">7</biological-state-id>
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                <id type="integer">140637</id>
                <biological-state-id type="integer">828</biological-state-id>
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                <id type="integer">140643</id>
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                <id type="integer">140999</id>
                <biological-state-id type="integer">73</biological-state-id>
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                <id type="integer">141687</id>
                <biological-state-id type="integer">67</biological-state-id>
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                <id type="integer">142395</id>
                <biological-state-id type="integer">1014</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">142871</id>
                <biological-state-id type="integer">1055</biological-state-id>
              </element-state>
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                <id type="integer">142911</id>
                <biological-state-id type="integer">1058</biological-state-id>
              </element-state>
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                <id type="integer">142955</id>
                <biological-state-id type="integer">1033</biological-state-id>
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                <id type="integer">142980</id>
                <biological-state-id type="integer">1071</biological-state-id>
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                <id type="integer">143430</id>
                <biological-state-id type="integer">1144</biological-state-id>
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                <id type="integer">145487</id>
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                <id type="integer">145524</id>
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              </element-state>
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                <id type="integer">145544</id>
                <biological-state-id type="integer">1428</biological-state-id>
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              <element-state>
                <id type="integer">145563</id>
                <biological-state-id type="integer">1436</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">145589</id>
                <biological-state-id type="integer">1367</biological-state-id>
              </element-state>
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                <id type="integer">145598</id>
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              </element-state>
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                <id type="integer">145604</id>
                <biological-state-id type="integer">1361</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">145612</id>
                <biological-state-id type="integer">1444</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">145642</id>
                <biological-state-id type="integer">1000</biological-state-id>
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                <id type="integer">146528</id>
                <biological-state-id type="integer">348</biological-state-id>
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                <id type="integer">146637</id>
                <biological-state-id type="integer">1592</biological-state-id>
              </element-state>
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              </element-state>
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                <biological-state-id type="integer">1609</biological-state-id>
              </element-state>
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                <id type="integer">146801</id>
                <biological-state-id type="integer">1658</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">146911</id>
                <biological-state-id type="integer">665</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">146932</id>
                <biological-state-id type="integer">566</biological-state-id>
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              <element-state>
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                <biological-state-id type="integer">1674</biological-state-id>
              </element-state>
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                <id type="integer">149714</id>
                <biological-state-id type="integer">1534</biological-state-id>
              </element-state>
            </element-states>
          </protein>
          <protein>
            <id type="integer">2713</id>
            <name>Voltage-dependent N-type calcium channel subunit alpha-1B</name>
            <uniprot-id>Q00975</uniprot-id>
            <description>Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin- IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons</description>
            <hmdbp-id>HMDBP07492</hmdbp-id>
            <gene-name>CACNA1B</gene-name>
            <locus>9q34</locus>
            <drugbank-id nil="true"/>
            <genbank-id>M94173</genbank-id>
            <species-id type="integer">1</species-id>
            <ec-numbers></ec-numbers>
            <synonyms nil="true"/>
            <element-states>
              <element-state>
                <id type="integer">136373</id>
                <biological-state-id type="integer">74</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">139856</id>
                <biological-state-id type="integer">204</biological-state-id>
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              <element-state>
                <id type="integer">140828</id>
                <biological-state-id type="integer">73</biological-state-id>
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              <element-state>
                <id type="integer">141881</id>
                <biological-state-id type="integer">787</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">142899</id>
                <biological-state-id type="integer">1058</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">142954</id>
                <biological-state-id type="integer">1033</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">142979</id>
                <biological-state-id type="integer">1071</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">143080</id>
                <biological-state-id type="integer">901</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">143190</id>
                <biological-state-id type="integer">1118</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">143261</id>
                <biological-state-id type="integer">52</biological-state-id>
              </element-state>
              <element-state>
                <id type="integer">143418</id>
                <biological-state-id type="integer">308</biological-state-id>
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              </element-state>
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                <biological-state-id type="integer">1428</biological-state-id>
              </element-state>
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                <biological-state-id type="integer">1436</biological-state-id>
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              </element-state>
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                <biological-state-id type="integer">1592</biological-state-id>
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                <biological-state-id type="integer">1563</biological-state-id>
              </element-state>
            </element-states>
          </protein>
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          <protein-complex>
            <id type="integer">368</id>
            <name>Histidine decarboxylase</name>
            <species-id type="integer">1</species-id>
            <pwp-id>PW_P000368</pwp-id>
            <protein_complex-proteins>
              <protein-complex-protein>
                <id type="integer">390</id>
                <protein-id type="integer">828</protein-id>
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            </protein_complex-proteins>
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              <protein-complex-cofactor>
                <id type="integer">170</id>
                <compound-id type="integer">1148</compound-id>
                <stoichiometry type="integer">1</stoichiometry>
              </protein-complex-cofactor>
            </protein_complex-cofactors>
          </protein-complex>
          <protein-complex>
            <id type="integer">14358</id>
            <name>vesicular monoamine transporter 2</name>
            <species-id type="integer">1</species-id>
            <pwp-id>PW_P014358</pwp-id>
            <protein_complex-proteins>
              <protein-complex-protein>
                <id type="integer">24302</id>
                <protein-id type="integer">1957</protein-id>
                <stoichiometry type="integer" nil="true"/>
              </protein-complex-protein>
            </protein_complex-proteins>
          </protein-complex>
          <protein-complex>
            <id type="integer">6635</id>
            <name>Histamine H1 receptor</name>
            <species-id type="integer">1</species-id>
            <pwp-id>PW_P006635</pwp-id>
            <protein_complex-proteins>
              <protein-complex-protein>
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                <protein-id type="integer">2116</protein-id>
                <stoichiometry type="integer" nil="true"/>
              </protein-complex-protein>
            </protein_complex-proteins>
          </protein-complex>
          <protein-complex>
            <id type="integer">15239</id>
            <name>Calcium channel</name>
            <species-id type="integer">1</species-id>
            <pwp-id>PW_P015239</pwp-id>
            <protein_complex-proteins>
              <protein-complex-protein>
                <id type="integer">25359</id>
                <protein-id type="integer">2705</protein-id>
                <stoichiometry type="integer" nil="true"/>
              </protein-complex-protein>
              <protein-complex-protein>
                <id type="integer">25360</id>
                <protein-id type="integer">2706</protein-id>
                <stoichiometry type="integer" nil="true"/>
              </protein-complex-protein>
              <protein-complex-protein>
                <id type="integer">25361</id>
                <protein-id type="integer">2713</protein-id>
                <stoichiometry type="integer" nil="true"/>
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                <id type="integer">141883</id>
                <biological-state-id type="integer">787</biological-state-id>
              </element-state>
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        </protein-complexes>
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            <spontaneous type="boolean">false</spontaneous>
            <pwr-id>PW_R000213</pwr-id>
            <direction>Right</direction>
            <reaction-left-elements>
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