CHOLINE is a basic constituent of lecithin that is found in many plants and animal organs. Choline was officially recognized as an essential nutrient by the Institute of Medicine in 1998.1 Its role in the body is complex. It is needed for neurotransmitter synthesis (acetylcholine), cell-membrane signaling (phospholipids), lipid transport (lipoproteins), and methyl-group metabolism (homocysteine reduction). It is the major dietary source of methyl groups via the synthesis of S-adenosylmethionine (AdoMet). At least 50 AdoMet-dependent reactions have been identified in mammals, and it is likely that the number is much higher. Choline is required to make the phospholipids phosphatidylcholine, lysophosphatidylcholine, choline plasmalogen, and sphingomyelin—essential components for all membranes. It plays important roles in brain and memory development in the fetus and appears to decrease the risk of the development of neural tube defects. The importance of choline in the diet extends into adulthood and old age. In a study of healthy adult subjects deprived of dietary choline, 77% of the men and 80% of the postmenopausal women developed signs of subclinical organ dysfunction (fatty liver or muscle damage). Less than half of premenopausal women developed such signs. Ten percent of the subjects studied developed fatty liver, muscle damage, or both when they consumed the Adequate Intake (AI) of choline. The damage was reversed when they consumed a high-choline diet. Plasma choline concentration has been found to vary in response to diet, decreasing approximately 30 percent in humans fed a choline-deficient diet for 3 weeks. Based on estimated dietary intakes and studies reporting liver damage with lower choline intakes, the Institute of Medicine, Food and Nutrition Board set the AI for choline at 425 milligrams/per day for women aged 19 and older, and 550 milligrams/per day for men aged 19 and older.

Tubocurarine, a naturally occurring alkaloid, is used to treat smoking withdrawl syndrom. Tubocurarine, the chief alkaloid in tobacco products, binds stereo-selectively to nicotinic-cholinergic receptors at the autonomic ganglia, in the adrenal medulla, at neuromuscular junctions, and in the brain. Two types of central nervous system effects are believed to be the basis of Tubocurarine's positively reinforcing properties. A stimulating effect is exerted mainly in the cortex via the locus ceruleus and a reward effect is exerted in the limbic system. At low doses the stimulant effects predominate while at high doses the reward effects predominate. Intermittent intravenous administration of Tubocurarine activates neurohormonal pathways, releasing acetylcholine, norepinephrine, dopamine, serotonin, vasopressin, beta-endorphin, growth hormone, and ACTH. Tubocurarine competes with acetylcholine for post-synaptic nicotinic NM receptors and blocks them.

HYDROCHLORIC ACID is formed by dissolving hydrogen chloride gas in water. It is a strong corrosive acid that is commonly used as a laboratory reagent. Also, it constitutes the majority of gastric acid, the human digestive fluid. Skin contact with HYDROCHLORIC ACID can cause redness, pain, and severe skin burns. It may cause severe burns to the eye and permanent eye damage.

Trimethylamine (or TMA) a tertiary amine, is synthesized by the action of microbial enzymes in humans. The decrease of TMA metabolism and excessive TMA excretion cause the disease trimethylaminuria and some other diseases associated with the abnormal level of TMA, e.g., obesity, diabetes, cardiovascular diseases. It was shown, that TMS is a full agonist of human trace amine-associated receptor 5, TAAR5. In addition, TMA is a precursor of N-oxide form, an emergent biomarker of human health that can lead to renal diseases, neurological disorders, and cancer.

Pirenzepine is a M1 muscarinic receptor antagonist, which is prescribed for the treatment of gastric and duodenal ulcer in Europe. The drug preferentially acts on the gastric mucosa to inhibit secretion of both gastric acid and pepsin. Experiment with healthy volunteers demonstrated that pirenzepine passes the blood-brain barrier, but only to a small extent.

Imidafenacin (KRP-197/ONO-8025) is the latest antimuscarinic (AM) developed for the treatment of overactive bladder syndrome (OAB) and, at the moment, it is marketed only in Japan. It has high affinities for the M3 and M1 muscarinic receptor subtypes, a low affinity for M2 receptors, and a potent inhibitory activity against rhythmic bladder contractions. Imidafenacin has excellent efficacy, tolerability, and safety. It is indicated for patients with nocturia, nocturnal polyuria, and benign prostatic hyperplasia.

Acotiamide (Acofide(®)), an oral first-in-class prokinetic drug, is under global development by Zeria Pharmaceutical Co. Ltd and Astellas Pharma Inc. for the treatment of patients with functional dyspepsia. The drug modulates upper gastrointestinal motility to alleviate abdominal symptoms resulting from hypomotility and delayed gastric emptying. It exerts its activity in the stomach via muscarinic receptor inhibition, resulting in enhanced acetylcholine release and inhibition of acetylcholinesterase activity. Acofide® is launched in Japan for treating functional dyspepsia.

Tropisetron (Tropisetron-AFT) is a potent and selective serotonin 3 (5-hydroxytryptamine3; 5-HT3) receptor antagonist with antiemetic properties, probably mediated via antagonism of receptors both at peripheral sites and in the central nervous system. Surgery and treatment with certain substances, including some chemotherapeutic agents, may trigger the release of serotonin from enterochromaffin-like cells in the visceral mucosa and initiate the emesis reflex and its accompanying feeling of nausea. Tropisetron (Tropisetron-AFT) selectively blocks the excitation of the presynaptic 5-HT3 receptors of the peripheral neurons in this reflex, and may exert additional direct actions within the CNS on 5-HT3 receptors mediating the actions of vagal input to the area postrema.

Doxepin is a dibenzoxepin tricyclic antidepressant marketed worldwide. It is a white crystalline solid readily soluble in water, lower alcohols and chloroform. The mechanism of action of doxepin is not definitely known. It is not a central nervous system stimulant nor a monoamine oxidase inhibitor. The current hypothesis is that the clinical effects are due, at least in part, to influences on the adrenergic activity at the synapses so that deactivation of norepinephrine by reuptake into the nerve terminals is prevented. Antidepressants may increase risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders. Drowsiness is the most commonly noticed side effect. This tends to disappear as therapy is continued. Other infrequently reported CNS side effects are confusion, disorientation, hallucinations, numbness, paresthesias, ataxia, extrapyramidal symptoms, seizures, tardive dyskinesia, and tremor. : Cardiovascular effects including hypotension, hypertension, and tachycardia have been reported occasionally. Skin rash, edema, photosensitization, and pruritus have occasionally occurred. Eosinophilia has been reported in a few patients. There have been occasional reports of bone marrow depression manifesting as agranulocytosis, leukopenia, thrombocytopenia, and purpura. Doxepin is used to treat depression, anxiety disorders, itchiness, trouble sleeping, and as a second-line treatment of chronic idiopathic urticaria (hives). Its oral formulations are FDA-approved for the treatment of depression, anxiety, and insomnia and its topical formulations are FDA-approved the short-term management (up to 8 days) of atopic dermatitis and lichen simplex chronicus. Whereas in Australia and the UK, the only licensed indication(s) is/are in the treatment of major depression and pruritus in eczema, respectively.