Bamidipine is an antihypertensive drug belonging to the dihydropyridine (DHP) group of calcium antagonists. The product was originally developed by Yamanouchi Pharmaceutical (Tokyo, Japan) and is currently marketed in Japan under the trade name of Hypoca (Astellas Pharma Inc, Tokyo, Japan). It is available in a modified-release formulation which has a gradual onset of action and is effective in a single daily oral dose of 10 to 20 mg. Bamidipine has selective action against cardiovascular calcium antagonist receptors and its antihypertensive action is related to the reduction of peripheral vascular resistance secondary to its vasodilatory action. The clinical antihypertensive efficacy of barnidipine is similar to that of other DHP calcium antagonists such as nitrendipine and amlodipine, and antihypertensives belonging to other drug classes such as atenolol and enalapril. Barnidipine has been found to be as efficacious and well tolerated as hydrochlorothiazide in the management of hypertension in elderly patients. Barnidipine is generally well tolerated. As with other DHP calcium antagonists, vasodilator adverse events such as headache, flushing and peripheral oedema account for most of the adverse events reported with its use and are usually transient. Oedema is less frequent than with amlodipine and nitrendipine. Its use is not associated with reflex tachycardia.

Linopirdine [DuP 996, 3, 3-bis(4-pyridinylmethyl)-1-phenylindolin-2-one], a putative cognition enhancing drug, increases acetylcholine release in rat brain tissue and improves performance in animal models of learning and memory. Linopirdine was developed as a cognitive enhancing molecule and demonstrated to specifically block the potassium current generated by the brain specific KCNQ2-KCNQ3 proteins (M-channel). Linopirdine also acts as an agonist of TRPV1. At low concentrations linopirdine sensitizes both recombinant and native TRPV1 channels to heat, in a manner that is not prevented by the Kv7-channel opener flupirtine. Taken together, these results indicate that linopirdine exerts an excitatory action on mammalian nociceptors not only through inhibition of the M current but also through activation of the capsaicin receptor TRPV1. In the late 1980s, DuPont initiated clinical trials with linopirdine for Alzheimer’s disease. Linopirdine was regarded as a promising drug because it enhanced the release of acetylcholine in cholinergic nerve terminals in the brain only when its release was triggered and improved learning and memory in rodents and primates. Although clinical trials with linopirdine remained largely inconclusive or showed that it did not improve memory performance in elderly subjects, linopirdine became a valuable pharmacological tool. Development of Linopirdine for the treatment of Alzheimer's disease was discontinued.

Fenoverine is a potent musculotropic, the anti-spasmodic agent that restores smooth muscle motility and relieves the distressing symptoms associated with irritable bowel syndrome (IBS) and primary dysmenorrhea. Fenoverine is a non-anticholinergic phenothiazine derivative that may also inhibit calcium channel currents. Fenoverine primarily affects the gastrointestinal tract, bile duct, and female genital organs. Fenoverine has been repeatedly implicated in the occurrence of rhabdomyolysis, a potentially fatal adverse effect, in France. Thes drug has been therefore unavailable in France since December 1995 but commonly used in the treatment of gastrointestinal spasmodic disorders in Taiwan.

Carisbamate is an experimental anticonvulsant drug that was under development by Johnson & Johnson Pharmaceutical Research and Development but never marketed. Acute and chronic nonclinical toxicological studies have not revealed any significant abnormalities other than dose-related CNS toxicity. Carisbamate displays high potency in a broad range of rodent seizure and epilepsy models at doses well below those that produce CNS toxicity. The exact mechanism of action is unknown but neuroprotective and antiseizure activity of Carisbamate likely results in part from decreased calcium accumulation through blockade of T-type Ca2+ channels. A phase II clinical trial in the treatment of partial seizures demonstrated that the compound has efficacy in the treatment of partial seizures and a good safety profile. In large multicenter phase III clinical trial for the treatment of partial seizures carisbamate at doses of 300, 800, and 1,600 mg/d was effective as adjunctive therapy for reducing the frequency of partial-onset seizures. The most common adverse events, encountered mainly at daily doses of 1000 mg or more, were CNS-related, including headache, dizziness, somnolence, and nausea. In another phase III clinical trial, carisbamate was not more efficacious in migraine prophylaxis than placebo, but carisbamate monotherapy was well tolerated at doses up to 600 mg per day. Johnson & Johnson received provisional approval by the FDA to market carisbamate under the brand name of Comfyde. However, on August 21, 2009, Johnson & Johnson reported that the FDA had failed to give marketing approval.

Metyridine has been shown to possess anthelmintic activity, particularly for the nematodes of the alimentary canal. Methyridine is able to pass freely through most of the barriers, which maintain body integrity. It produces neuromuscular block of the decamethonium type. There appears to be sufficient difference between the sensitivity of nematode and vertebrate nervous systems to this drug to allow a wide safety margin for its use in animals. Signs of toxicity, principally dullness and lassitude, may be produced by overdosage of the drug. When given subcutaneously methyridine may cause local pain, and swelling.

Bunazosin (E-643) is a quinazoline derivative with a1-adrenoceptor blocking activity. It has been clinically used both as a systemic antihypertensive as well as an ocular hypotensive drug. The major adverse effect associated with the use of bunazosin is orthostatic hypotension or its consequences (e.g. dizziness). Others adverse effects include headache, sweating, nausea, dry mouth, abdominal pain, diarrhea, and constipation. The effects of Bunazosin may be enhanced by diuretics and other antihypertensive agents and decreased by Rifampicin.

Levomethadyl acetate (LAAM) is a synthetic opioid agonist with actions qualitatively similar to morphine (a prototypic mu agonist) and affecting the central nervous system (CNS) and smooth muscle. Principal actions include analgesia and sedation. Tolerance to these effects develops with repeated use. An abstinence syndrome generally occurs upon cessation of chronic administration similar to that observed with other opiates, but with slower onset, more prolonged course, and less severe symptoms. LAAM exerts its clinical effects in the treatment of opiate abuse through two mechanisms. First, LAAM cross-substitutes for opiates of the morphinetype, suppressing symptoms of withdrawal in opiate-dependent individuals. Second, chronic oral administration of LAAM can produce sufficient tolerance to block the subjective “high” of usual doses of parenterally administered opiates. Since the introduction of levomethadyl in 1995, the manufacturer has received increasing reports of severe cardiac-related adverse events, including QT interval prolongation, Torsades de Pointes and cardiac arrest. Other cardiac-related adverse events have also been reported, including arrhythmias, syncope, and angina. These events led to the removal of levomethadyl from the European market in March 2001. A very small number of patients may benefit from levomethadyl, but the risk of continued distribution and use no longer outweighs the overall benefits.

Nitrendipine is a calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive. By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, nitrendipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

Aprindine is a class Ib antiarrhythmic agent. It is not approved in USA, but is available in European countries, where it is used to treat supraventricular and ventricular arrhythmias. Aprindine acts by blocking sodium voltage channels and disrupting interactions between calmodulin and prosphodiesterase.

Lidoflazine is a vasodilator used for the treatment of angina pectoris. Lidoflazine is a high-affinity blocker of the HERG K(+)channel.