Pathways

Pilocarpine is a muscarinic cholinergic agonist used on the eye to treat elevated intraocular pressure, various types of glaucoma, and to induce miosis. Also available orally to treat symptoms of dry mouth associated with Sjogren's syndrome and radiotherapy. When used to treat glaucoma it is administered as an eye drop. Pilocarpine is a slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. When applied topically to the eye as a single dose it causes miosis, spasm of accommodation, and may cause a transitory rise in intraocular pressure followed by a more persistent fall. Pilocarpine is a cholinergic parasympathomimetic agent. It increase secretion by the exocrine glands, and produces contraction of the iris sphincter muscle and ciliary muscle (when given topically to the eyes) by mainly stimulating muscarinic receptors. Stimulation of the M2 receptors specifically causes the contraction of the ciliary muscles of the eye.

Pilocarpine, commonly known as Isopto Carpine, is a muscarinic cholinergic agonist that regularly comes as an eye drop for intraocular pressure, Glaucoma, or to induce miosis. Pilocarpine is an agonist of muscarinic acetylcholine receptors subtype M1, M2, and M3. It is also a partial agonist for M4 muscarinic acetylcholine receptor. However approximately 60% to 75% of muscarinic acetylcholine receptors in the ciliary and iris sphincter muscles of the eye are the M3 subtype. By activating these receptors, the iris and ciliary muscles contract causing miosis, spasm of accommodation, and may cause a rise in intraocular pressure followed by a persistent fall. Muscarinic acetylcholine receptors M3 are coupled to the Gq signaling cascade. The activation of this leads to the acitvation of phospholipase C, which converts Phosphatidylinositol (3,4,5)-trisphosphate to inositol (3,4,5)-trisphosphate (IP3) and diacylglycerol (DAG). IP3 activates IP3 receptors on the sarcoplasmic reticulum leading to the release of stored calcium into the cytosol. DAG activates protein kinase C (PKC). One of the downstream effects of PKC include activation of calcium channels on the membrane, leading to influx of calcium ions into the cytosol. Both IP3 and DAG increase cytosolic levels of calcium which then binds to calmodulin to create a calcium-calmodulin complex. Muscle contraction and relaxation are controlled by the enzymes myosin kinase and myosin phosphatase. Myosin kinase phosphorylates myosin light chain, leading to interaction between actin and myosin, producing muscle contraction. Myosin phosphorylase dephosphorylates the phosphorylated myosin light chain, preventing interaction with actin, producing muscle relaxation. The calcium-calmodulin activates myosin kinase, leading to increased phosphorylation of myosin light chain and more muscle contraction. The activation of muscarinic acetylcholine receptor M3 continues to activate myosin kinase which leads to continued contractions of the ciliary or iris sphincter muscles. Pilocarpine is also an agonist of the muscarinic acetylcholine receptors M1, M2, and M4, however, they are much less present within the ciliary and iris sphincter muscles. M1 is also Gq coupled so has the same mechanism. M2 and M4 inhibit Adenylate cyclase, but that is not important in the contraction of the eye muscles. Pilocarpine is also only a partial agonist of M4. Pilocarpine is typically administered as an opyhalmalic solution, but comes in tablet form as well. Some side effects of using pilocarpine may include cheat pain, fainting, headache, and nausea.

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

Pimethixene is a thioxanthene H1-antihistamine. 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.

Pimozide is a member of the class of benzimidazoles that is 1,3-dihydro-2H-benzimidazol-2-one in which one of the nitrogens is substituted by a piperidin-4-yl group, which in turn is substituted on the nitrogen by a 4,4-bis(p-fluorophenyl)butyl group. It has a role as a H1-receptor antagonist, a serotonergic antagonist, a first generation antipsychotic, an antidyskinesia agent and a dopaminergic antagonist. It is a member of benzimidazoles, an organofluorine compound and a heteroarylpiperidine.Pimozide is an orally active antipsychotic drug product which shares with other antipsychotics the ability to blockade dopaminergic receptors on neurons in the central nervous system. The ability of pimozide to suppress motor and phonic tics in Tourette's Disorder is thought to be primarily a function of its dopaminergic blocking activity. Pimozide binds and inhibits the dopamine D2 receptor in the CNS.

Metabolites of Pimozide are predicted with biotransformer.