Pizotifen (INN) or pizotyline (USAN), trade name Sandomigran, is a benzocycloheptene-based drug used as a medicine, primarily as a preventative to reduce the frequency of recurrent migraine headaches. Pizotifen is a serotonin antagonist acting mainly at the 5-HT2A and 5HT2C receptors. It also has some activity as an antihistamine as well as some anticholinergic activity. The main medical use for pizotifen is for the prevention of vascular headache including migraine and cluster headache. Pizotifen is one of a range of medications used for this purpose, other options include propranolol, topiramate, valproic acid and amitriptyline. While pizotifen is reasonably effective, its use is limited by side effects, principally drowsiness and weight gain, and it is usually not the first choice medicine for preventing migraines, instead being used as an alternative when other drugs have failed to be effective. It is not effective in relieving migraine attacks once in progress. Pizotifen has also been reported as highly effective in a severe case of erythromelalgia, a rare neurovascular disease that is sometimes refractory to the other drugs named above. Side effects include sedation, dry mouth, drowsiness, increased appetite and weight gain. Occasionally it may cause nausea, headaches, or dizziness. In rare cases, anxiety, aggression and depression may also occur. Pizotifen is well absorbed from the gastro-intestinal tract, peak plasma concentrations occurring approximately 5 hours after oral administration. The absorption of pizotifen is fast (absorption half life 0.5 to 0.8 hours) and nearly complete (80%). Over 90% is bound to plasma proteins. Pizotifen undergoes extensive metabolism. Over half of a dose is excreted in the urine, chiefly as metabolites; a significant proportion is excreted in the faeces. The primary metabolite of pizotifen (N-glucuronide conjugate) has a long elimination half-life of about 23 hours.

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.

Octopamine is an organic chemical closely related to norepinephrine. In many types of invertebrates it functions as a neurotransmitter. Octopamine is known to exert adrenergic effects in mammals although specific octopamine receptors have been cloned only in invertebrates. It has been shown that octopamine can stimulate alpha(2)-adrenoceptors (ARs) in Chinese hamster ovary cells transfected with human alpha(2)-ARs. Octopamine stimulates lipolysis through beta(3)-rather than beta(1)-or beta(2)-AR activation in white adipocytes from different mammalian species. Octopamine activates only beta(3)-ARs and is devoid of alpha(2)-adrenergic agonism. Thus, octopamine could be considered as an endogenous selective beta(3)-AR agonist. In humans Octopamine is a trace amine found endogenously in the human brain where it interacts with signalling of catecholamines; it is structurally similar to synephrine and tyramine, being a metabolite of the latter (via dopamine β-hydroxylase) and substrate for the synthesis of the former (via phenethanolamine N-methyltransferase[3]) while being perhaps the closest in structure to noradrenaline. Octopamine is found in the bitter orange similar to many biogenic amines related to L-tyrosine that are used as dietary supplements, this includes synephrine and hordenine. p-Octopamine HCl (Norphen) was studied in the late 1960’s and 1970’s as a drug for the treatment of hypotensive regulatory and circulatory disorders. Octopamine was used as a nootropic. All optical isomers (enantiomers) of octopamine are on the World Anti-Doping Agency (WADA) 2014 list of substances prohibited in competition.

Laninamivir ocatanoate is a prodrug of Laninamivir (R-125489), a new neuraminidase (NA) inhibitor, was discovered, and in this study, its NA inhibitory activities against various influenza viruses including oseltamivir-resistant viruses are reported. Laninamivir octanoate has been approved for use in Japanese clinics for the treatment and prevention of influenza in both adults and children. The inhaled laninamivir octanoate is converted into its active form, laninamivir, in the lungs where a high concentration persists for a long period of time.

Ethamsylate (2,5-dihydroxy-benzene-sulfonate diethylammonium salt) is a synthetic hemostatic drug indicated in cases of capillary bleeding. Ethamsylate acts on the first step of hemostasis by improving platelet adhesiveness and restoring capillary resistance. In addition it inhibits prostaglandin biosynthesis. Well-controlled clinical trials clearly showed the therapeutic efficacy of ethamsylate in dysfunctional uterine bleeding, with the magnitude of blood-loss reduction being directly proportional to the severity of the menorrhagia. Other well-controlled clinical trials showed therapeutic efficacy of ethamsylate in periventricular hemorrhage in very low birth weight babies and surgical or postsurgical capillary bleeding.

Caroverine is a spasmolytic drug used in tinnitus treatment improves mechanosensitivity and mechanotransduction phenomenon and otoneuroprotective agent. Caroverine acts as an N-type calcium channel blocker, competitive AMPA receptor antagonist, and non-competitive NMDA receptor antagonist. When excessive glutamate binds to NMDA receptors, the receptor opens and allows calcium and sodium to enter the neuron, abnormal levels of calcium disturbs ionic balance causing spontaneous depolarization state. Pathological spontaneous depolarization state is reversed back to physiological polarization state by antagonistic property of Caroverine.

Clocapramine is a chlorinated derivative of carpipramine. The hydrochloride has been given orally in the treatment of schizophrenia. Clocapramine is an antagonist of the Dopamine D2 and Serotonine (5-HT2) receptors. It has been implicated in at least one strange death, including a suicide. It augments the paroxetine in the panic disorder treatment.

Cycotiamine is a derivative of tiamine that was developed in Japan and used for the treatment of neurogenic bladder.

Sarpogrelate (brand name Anplag; former developmental code names MCI-9042, LS-187,118) is a drug which acts as an antagonist at the 5HT2A and 5-HT2B receptors. It blocks serotonin-induced platelet aggregation and has applications in the treatment of many diseases including diabetes mellitus, Buerger's disease, Raynaud's disease, coronary artery disease, angina pectoris, and atherosclerosis.

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.