Browsing Pathways

Amifampridine, also known as Firdapse, is a presynaptic voltage-gated potassium channel blocker. This drug is used to treat Lambert-Eaton myasthenic syndrome. LEMS is an auto-immune disorder of the neuromuscular junction that is characterized by proximal muscle weakness, depressed tendon reflexes, and posttetanic potentiation in addition to autonomic dysfunction. This drug blocks presynaptic fast voltage-gated potassium channels, which prolongs the action potential and increases presynaptic calcium concentrations while increasing the acetylcholine concentrations at the neuromuscular junction. Increased intracellular calcium enhances the exocytosis of acetylcholine-containing vesicles and enhances impulse transmission at the synapses. It is administered as an oral tablet.

Dolasetron is a selective serotonin 5-HT3 receptor antagonist. In vivo, the drug is rapidly converted into its major active metabolite, hydrodolasetron, which seems to be largely responsible for the drug's pharmacological activity. The antiemetic activity of the drug is brought about through the inhibition of 5-HT3 receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT3 receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone.

Donepezil is an acetylcholinesterase inhibitor also known as Adlarity, Aricept and Namzaric, that is used in the treatment of Alzheimer's Disease and dementia. It is administered orally or transdermally, sometimes in combination with memantine in order to treat moderate to severe dementia. Donepezil selectively inhibits the acetylcholinesterase enzyme, by doing so it is believed to enhance cholinergic transmission to relieve the symptoms of Alzheimer's and dementia. Normally acetylcholinesterase breaks down acetylcholine, this inhibited its enhances cholinergic transmission. Donepezil goes through first-pass metabolism by CYP3A4 and CYP2D6 into metabolites which can be further broken down by dealkylation, hydroxylation, oxidation, hydrolysis and glucuronidation.

Dosulepin is indicated in the treatment of symptoms of depressive illness, especially where an anti-anxiety effect is required. Dosulepin displays affinity towards α2-adrenoceptors and to a lesser extent, α1-adrenoceptors. Inhibition of presynaptic α2-adrenoceptors by dosulepin facilitates noradrenaline release and further potentiates the antidepressant effects. It also downregulates central β-adrenoceptors by causing a decline in the number of receptors and reduces noradrenaline-induced cyclic AMP formation. Dosulepin binds to 5HT1A and 5HT2A receptors in the cerebral cortex and hippocampus as an antagonist. 5HT1A receptors are autoreceptors that inhibit 5HT release and 5HT2A receptors are Gi/Go-coupled receptors that reduces dopamine release upon activation. Antagonism at 5HT2A receptors may also improve sleep patterns. Dosulepin also binds to muscarinic acetylcholine receptors and causes antimuscarinic side effects such as dry mouth. By acting as an antagonist at histamine type 1 (H1) receptors, dosulepin mediates a sedative effect.

Progesterone is a hormone naturally occurring in females. This molecule is essential for endometrial receptivity, embryo implantation, and the successful establishment of pregnancy. It is used as an oral drug as a contraceptive to prevent ovulation and fertilization in certain formulations, as well as a promoter/supporter of pregnancy in other formulations. Pharmaceutical progesterone is made from a plant source as a starting material and is chemically identical to progesterone of human ovarian origin. Progesterone binds its receptor (located both on the membrane and in the cytosol) which activates a signaling pathway resulting in a lower release of GnRH by the hypothalamus. The lower concentration of GnRH results in the transcription of less LH and FSH hormones by the pituitary gland. The overall effect is that the ovaries can't release an egg (no ovulation) and the cervical mucus thicken to be unfavorable for sperm penetration. This drug is administered as an oral tablet/capsule for contraception and as a vaginal gel/insert to maintain the pregnancy.

The biosynthesis of ursocholic acid, a secondary bile acid, is closely associated with the enzymatic activities encoded by the hdh operon in Clostridium absonum. This operon includes two contiguous genes: hdhA, encoding the 7α-hydroxysteroid dehydrogenase (7α-HSDH), and hdhB, coding for the 7β-hydroxysteroid dehydrogenase (7β-HSDH). The process begins with the enzyme 7α-HSDH, which catalyzes the oxidation of cholic acid (CA) at the 7α-hydroxy position, converting it into a 7-keto intermediate. Subsequently, the 7β-HSDH reduces this keto intermediate, but in a stereoselective manner that introduces a 7β-hydroxy group, resulting in the formation of ursocholic acid. The operon appears to be co-regulated, facilitating a coordinated response to bile acids, with promoter and regulatory sequences identified upstream of hdhA and hdhB. The biosynthetic pathway mediated by this operon exemplifies a stereospecific transformation that alters the aromatic configuration of bile acids, enabling bacteria like C. absonum to produce functionally diverse secondary bile acids such as ursocholic acid, which play pivotal roles in host-microbiome interactions and possess potential therapeutic properties.

Gadoversetamide is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Gadoversetamide passes through the liver and is then excreted from the body mainly through the kidney.

1,2-Benzodiazepine is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. 1,2-Benzodiazepine passes through the liver and is then excreted from the body mainly through the kidney.