Pathways

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.

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

Pinaverium is a spasmolytic agent used for the symptomatic treatment of irritable bowel syndrome (IBS) and functional disorders of the biliary tract. It can be found under the brand name Dicetel. Pinaverium is a spasmolytic agent used for functional gastrointestinal disorders. It is a quaternary ammonium compound that acts as an atypical calcium antagonist to restore normal bowel function. It is shown to relieve GI spasm and pain, transit disturbances and other symptoms related to motility disorders and may be considered as effective first-lline therapy for patients with irritable bowel syndrome (IBS). Pinaverium bromide is the common ingredient in formulations, mostly as oral tablets. Pinaverium is a selective and specific voltage-dependent calcium channel blocker located on intestinal smooth muscle cells to inhibit calcium influx. It mediates various effects on the GI tract: it causes oesophageal, gastric and duodenal relaxation, relaxes the colon and intestines, inhibits colonic motility in response to food, hormonal or pharmacological stimuli, accelerates gastric emptying, and reduces contractions of the gallbladder and phasic contractions of sphincter of Oddi. Pinaverium interacts with the 1,4-dihydropyridine binding sites on voltage dependent L-type calcium channels located on GI smooth muscle cells in a competitve manner. The binding site is located in the alpha 1S subunit and pinaverium most likely antagonizes the action of calcium ions by stabilizing a non-conducting channel state. Pinaverium inhibits smooth muscle contractions of the GI tract by inhibiting inward calcium current and calcium influx. It is suggested that pinaverium may be able to bind to both closed or inactivates states of the calcium channel with similar affinity. Pinaverium is administered as an oral tablet. Possible side effects of using pinaverium may include stomach pain, heartburn, dry mouth, and headache.

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

Pindolol (also known as Visken) a beta blocker (non-selective) that block beta-1 adrenergic receptor in heart. Blocking beta-1 adrenergic receptor could prevent the binding of epinephrine and norepinephrine, which could efficiently reduce blood pressure and heart rate. In the juxtaglomerular apparatus, pindolol can also bind to beta-2 receptors to prevent the production and release of renin (also known as angiotensinogenase). Without renin, angiotensin II and aldosterone could not be produced, which ultimately prevent water retention and vasoconstriction.

Pindolol is a non-selective beta blocker. It can be administered orally, where it passes through hepatic portal circulation, and enters the bloodstream and travels to act on cardiomyocytes. In bronchial and vascular smooth muscle, pindolol can compete with epinephrine for beta-2 adrenergic receptors. By competing with catecholamines for adrenergic receptors, it inhibits sympathetic stimulation of the heart. The reduction of neurotransmitters binding to beta receptor proteins in the heart inhibits adenylate cyclase type 1. Because adenylate cyclase type 1 typically activates cAMP synthesis, which in turn activates PKA production, which then activates SRC and nitric oxide synthase, its inhibition causes the inhibition of cAMP, PKA, SRC and nitric oxide synthase signaling. Following this chain of reactions, we see that the inhibition of nitric oxide synthase reduces nitric oxide production outside the cell which results in vasoconstriction. On a different end of this reaction chain, the inhibition of SRC in essence causes the activation of Caspase 3 and Caspase 9. This Caspase cascade leads to cell apoptosis. The net result of all these reactions is a decreased sympathetic effect on cardiac cells, causing the heart rate to slow and arterial blood pressure to lower; thus, pindolol administration and binding reduces resting heart rate, cardiac output, afterload, blood pressure and orthostatic hypotension. By prolonging diastolic time, it can prevent re-infarction. One potentially less than desirable effect of non-selective beta blockers like pindolol is the bronchoconstrictive effect exerted by antagonizing beta-2 adrenergic receptors in the lungs. Clinically, it is used to increase atrioventricular block to treat supraventricular dysrhythmias. Pindolol also reduce sympathetic activity and is used to treat hypertension, angina, migraine headaches, and hypertrophic subaortic stenosis.

Pindolol is a beta adrenoceptor antagonist used to treat hypertension, edema, ventricular tachycardias, and atrial fibrillation. It can be found under the brand names Viskazide and Visken. Pindolol is a first generation non-selective beta blocker used in the treatment of hypertension. Early research into the use of pindolol found it had chronotropic effects, and so further investigation focused on the treatment of arrhythmia. Blocking beta-1 adrenergic receptors in the heart results in decreased heart rate and blood pressure. Beta-1 receptors are G-protein-coupled receptors (specifically Gs alpha subunit) whose action is exerted through the cyclic AMP (cAMP) and cAMP-dependent protein kinase action with resultant calcium ion concentration increases. Increased intracellular calcium increase inotropy in the heart through calcium-induced exchange facilitated by the sarcoplasmic reticulum. Myosin light chains phosphorylated by PKA lead to contractility in muscle cells. Normally, activation of the beta-1 receptor in the heart increases sinoatrial (SA) nodal, atrioventricular (AV) nodal, and ventricular muscular firing, which leads to increased heart rate and contractility. Stroke volume and cardiac output will also increase as a result. In the kidney, renin is released when smooth muscle cells in the juxtaglomerular apparatus are activated. Blood volume is eventually increased because of the downstream production of angiotensin II and aldosterone production triggered by renin. Ordinarily, this adrenergic response results in increased inotropy, chronotropy, and dromotropy. The blockade of this pathway with beta-1 blockers results in decreased contractility (inotropy), decreased heart rate (chronotropy), increased relaxation (lusitropy), and decreased cardiac conduction times (dromotropy).