Pathways

Metipranolol is a cardioselective 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, metipranolol 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, metipranolol 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 metipranolol 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. Metipranolol also reduce sympathetic activity and is used to treat ocular hypertension or open-angle glaucoma.

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

Metoclopramide is a dopamine receptor antagonist and has been approved by the FDA to treat nausea and vomiting in patients with gastroesophageal reflux disease or diabetic gastroparesis by increasing gastric motility.. Metoclopramide works by antagonizing central and peripheral dopamine-two receptors (D2) in the medullary chemoreceptor trigger zone in the area postrema, usually stimulated by levodopa or apomorphine. It achieves this by decreasing the sensitivity of visceral afferent nerves that transmit from the gastrointestinal system to the vomiting center in the area postrema in the chemoreceptor trigger zone. In addition to antagonizing dopamine receptors, metoclopramide is an antagonist at 5HT3 (type 3 serotonin receptors) and an agonist at 5HT4 receptors. Metoclopramide also blocks the antiperistaltic effects of apomorphine, allowing metoclopramide to slow apomorphine's inhibition of gastric emptying, thereby accelerating gastric emptying by increasing the amplitude and duration of esophageal contractions. Consequently, it increases the resting tone of the lower esophageal sphincter while simultaneously relaxing the duodenal bulb and pyloric sphincter, thereby increasing the peristalsis of the duodenum and jejunum.

Metoclopramide is a dopamine receptor antagonist and has been approved by the FDA to treat nausea and vomiting in patients with gastroesophageal reflux disease or diabetic gastroparesis by increasing gastric motility.. Metoclopramide works by antagonizing central and peripheral dopamine-two receptors (D2) in the medullary chemoreceptor trigger zone in the area postrema, usually stimulated by levodopa or apomorphine. It achieves this by decreasing the sensitivity of visceral afferent nerves that transmit from the gastrointestinal system to the vomiting center in the area postrema in the chemoreceptor trigger zone. In addition to antagonizing dopamine receptors, metoclopramide is an antagonist at 5HT3 (type 3 serotonin receptors) and an agonist at 5HT4 receptors. Metoclopramide's agonism of 5-HT4 receptors in the gastrointestinal tract can stimulate gastrointestinal motility, including enhancing gastric emptying and promoting peristalsis. This effect can be beneficial in conditions associated with delayed gastric emptying, such as gastroparesis, and it may help relieve symptoms like nausea and vomiting. Activation of 5-HT4 receptors can also lead to the release of acetylcholine, which further enhances smooth muscle contraction in the gut. In the gastrointestinal tract, when serotonin (5-HT) binds to 5-HT4 receptors in the GI tract, it initiates intracellular signaling through a G-protein-coupled mechanism. 5-HT4 receptors are typically coupled to Gs proteins. Activation of Gs proteins stimulates adenylate cyclase (AC), leading to increased production of cyclic AMP (cAMP) from ATP. The increase in cAMP levels activates protein kinase A (PKA) through the cAMP-PKA pathway. PKA activation can lead to smooth muscle contraction in the GI tract. This increased contractility promotes peristalsis and enhances gastric emptying by propelling food and digestive contents through the GI tract.

Metoclopramide is a dopamine receptor antagonist and has been approved by the FDA to treat nausea and vomiting in patients with gastroesophageal reflux disease or diabetic gastroparesis by increasing gastric motility.. Metoclopramide works by antagonizing central and peripheral dopamine-two receptors (D2) in the medullary chemoreceptor trigger zone in the area postrema, usually stimulated by levodopa or apomorphine. It achieves this by decreasing the sensitivity of visceral afferent nerves that transmit from the gastrointestinal system to the vomiting center in the area postrema in the chemoreceptor trigger zone. In addition to antagonizing dopamine receptors, metoclopramide is an antagonist at 5HT3 (type 3 serotonin receptors) and an agonist at 5HT4 receptors. Metoclopramide's agonism of 5-HT4 receptors in the gastrointestinal tract can stimulate gastrointestinal motility, including enhancing gastric emptying and promoting peristalsis. This effect can be beneficial in conditions associated with delayed gastric emptying, such as gastroparesis, and it may help relieve symptoms like nausea and vomiting. Activation of 5-HT4 receptors can also lead to the release of acetylcholine, which further enhances smooth muscle contraction in the gut. In the gastrointestinal tract, when serotonin (5-HT) binds to 5-HT4 receptors in the GI tract, it initiates intracellular signaling through a G-protein-coupled mechanism. 5-HT4 receptors are typically coupled to Gs proteins. Activation of Gs proteins stimulates adenylate cyclase (AC), leading to increased production of cyclic AMP (cAMP) from ATP. The increase in cAMP levels activates protein kinase A (PKA) through the cAMP-PKA pathway. PKA activation can lead to smooth muscle contraction in the GI tract. This increased contractility promotes peristalsis and enhances gastric emptying by propelling food and digestive contents through the GI tract.

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