Pathways

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.

Clomipramine is a dibenzazepine-derivative tricyclic antidepressant. Clomipramine may be used to treat obsessive-compulsive disorder (OCD) and disorders with an obsessive-compulsive component (e.g. depression, schizophrenia, Tourette's disorder). Clomipramine works by inhibiting seretonin reuptake, therefore increasing the seretonin levels. Administrated Clomipramine is quickly enters the blood stream and 98% becomes bound to plasma protein. Because of this and Clomipramine's lipophilic properties, Clomipramine has a large volume of distribution.

Clomocycline is a tetracycline antibiotic that inhibits bacterial cell growth by inhibiting translation. Clomocycline is lipophilic and easily diffuses across cell membranes or enters cells via porin channels in the bacterial membrane. It binds to the 30S ribosomal subunit and prevents the aminoacyl tRNA from binding to the A site of the ribosome-RNA complex. Clomocycline binding is reversible in nature. Clomocycline may be used to treat acne, gum disease, and other bacterial infections such as chalmydia, brucellosis, bartonellosis and cholera. Clomocycline is also effective against certain strains of malaria and may also be prescribed for the treatment of Lyme disease.

Clomocycline is a tetracycline used to treat bacterial infections. It is used for the treatment and management of Brucellosis, mycoplasma infection, acne vulgaris, chlamydial infection; chronic bronchitis. Clomocycline inhibits cell growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. The binding is reversible in nature. Clomocycline is lipophilic and can easily pass through the cell membrane or passively diffuses through porin channels in the bacterial membrane.