Pathways

Chlophedianol is an H1-antihistamine cough suppressant. 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. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. 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. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage. Clofedanol also inhibits the H1 histamine receptor on bronchiole smooth muscle myocytes. This normally activates the Gq signalling cascade which activates phospholipase C which catalyzes the production of Inositol 1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG). Because of the inhibition, IP3 doesn't activate the release of calcium from the sarcoplasmic reticulum, and DAG doesn't activate the release of calcium into the cytosol of the endothelial cell. This causes a low concentration of calcium in the cytosol, and it, therefore, cannot bind to calmodulin.Calcium bound calmodulin is required for the activation of myosin light chain kinase. This prevents the phosphorylation of myosin light chain 3, causing an accumulation of myosin light chain 3. This causes muscle relaxation, opening up the bronchioles in the lungs, making breathing easier.

Chlophedianol is an H1-antihistamine cough suppressant. 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. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage. Chlophedianol inhibits the H1 histamine receptor on blood vessel endothelial cells. This normally activates the Gq signalling cascade which activates phospholipase C which catalyzes the production of Inositol 1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG). Because of the inhibition, IP3 doesn't activate the release of calcium from the sarcoplasmic reticulum, and DAG doesn't activate the release of calcium into the cytosol of the endothelial cell. This causes a low concentration of calcium in the cytosol, and it, therefore, cannot bind to calmodulin. Calcium bound calmodulin is required for the activation of the calmodulin-binding domain of nitric oxide synthase. The inhibition of nitric oxide synthesis prevents the activation of myosin light chain phosphatase. This causes an accumulation of myosin light chain-phosphate which causes the muscle to contract and the blood vessel to constrict, decreasing the swelling and fluid leakage from the blood vessels caused by allergens.

Chlophedianol is an H1-antihistamine cough suppressant. 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. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. 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. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.

Clofibrate is a fibric acid derivative used to treat hypertriglyceridemia and high cholesterol. Clofibrate acts in the nucleus where is activates the peroxisome proliferator-activated receptor alpha (PPARα). PPARα binds to the retinoic acid receptor alpha (RXRα). This PPARα-RXRα complex regulate gene transcription/translation of proteins and enzymes involved lipolysis, fatty acid transport and biosynthesis, vLDL and HDL synthesis. Fatty acid biosynthesis is decreased due to the decrease expression of the enzyme acetyl-coA carboxylase. This enzyme is involved in one of the first steps in fatty acid synthesis by converting acetyl-coA to malonyl coA. Fatty acid uptake from the plasma into the liver is increased. This is because there is an upregulation of the fatty acid transporter. This decreases the amount of circulating fatty acids. Fatty acid metabolism is also increased due to upregulation of acyl coA synthase, an enzyme involved in fatty acid oxidation. These 3 alterations ultimately decrease fatty acids in the body, making less fatty acids available for triglyceride synthesis. Clofibrate also increases HDL synthesis by upregulating apolipoprotein A1 (APOA1) and apolipoproteins A2 (APOA2), which forms part of HDL. HDL is considered good cholesterol. VLDL and LDL are considered bad cholesterol. These levels are decreased due to downregulation of APOB which forms part of triglyceride-rich vLDL and LDL. Finally, triglyceride levels are decreased by 30%-60% via upregulation of lipoprotein lipase (LPL). LPL hydrolyses triglyceride, thus breaking it down. Other proteins that affect LPL are also altered. For instance, APOA5 activates LPL and it’s expression is increased with clofibrate. APOC3 inhibits lipolysis by inhibiting LPL, therefore, clofibrate decreases the expression of APOC3. Overall, clofibrate lowers LDL-C, total-C, triglycerides, and Apo B, while increasing HDL-C.

Metabolites of Clofibrate are predicted with biotransformer.

Clomipramine, also known as Anafranil, is a tricyclic antidepressant used in the treatment of obsessive-compulsive disorder and disorders with an obsessive-compulsive component, such as depression, schizophrenia, and Tourette’s disorder. This drug is the 3-chloro derivative of Imipramine. Clomipramine is a strong serotonin reuptake inhibitor (SRI), as the active main metabolite desmethyclomipramine (which is formed by N-demethylation of clomipramine via CYP2C19, 3A4, and 1A2) acts preferably as an inhibitor of noradrenaline reuptake. It blocks both sodium-dependent serotonin and sodium-dependent norepinephrine transporters from removing serotonin and norepinephrine respectively from the synaptic clefts in the brain. This allows an accumulation of the neurotransmitters. In consequence, it stimulates their receptors repeatedly increasing the signal of the receptors. α1-receptor blockage and β-down-regulation most likely play a role in the short-term effects of clomipramine. Clomipramine can be taken orally as a tablet or capsule.

Clomipramine is a tricyclic antidepressant classified as a serotonin-norepinephrine reuptake inhibitor (SNRI). It blocks both sodium dependent serotonin and sodium dependent norepinephrine transporters from removing serotonin and norepinephrine respectively from the synaptic cleft. This allows an accumulation of the neurotransmitters to stimulate their receptors repeatedly increasing the signal of the receptors. In depressed individuals serotonin and norepinephrine stimulation is low so an increase in serotonin and norepinephrine in the synapses can increase the stimulation of these receptors. The receptors that are being stimulated are 5-HT 2A, 2B, and 2C serotonin receptors and alpha 1 and beta 1 adrenergic receptors while clomipramine also desensitizes alpha 2 adrenergic receptors. Stimulation of the 2A, 2B and 3C receptor can increase cognitive abilities like learning, appetite, memory, mood and sleep. Sensitization of alpha A1 and beta B1 adrenergic receptors also improve cognitive function, fatigue, sleep and the immune system. It can also block histamine H1 receptors and muscarinic receptors which are the causes of the side effects like blurry vision, dry mouth and constipation experienced by those who take clomipramine. Clomipramine can be taken orally as a tablet or capsule to treat depression, OCD, schizophrenia and Tourettes.