Celivarone is a benzofuran derivative with a multifactorial mode of action including class IV Vaughan Williams’ electrophysiological as well as anti-adrenergic properties. It has no iodine and has a limited tissue accumulation compared with amiodarone. Celivarone exhibits effective anti-arrhythmic properties in several ventricular ischemia- or reperfusioninduced arrhythmia models as well as in in vitro and in vivo atrial fibrillation (AF) models. Its electrophysiological properties are similar to amiodarone (multifactorial mode of action) but with different relative effects on the ion channels. At the ventricular level, celivarone shows anti-arrhythmic activities by suppressing reperfusion-induced arrhythmias (i.v. and oral routes) and reducing the early mortality due to myocardial infarction (oral route) in rats models. At the atrial level, celivarone is effective in atrial fibrillation models with restoration of sinus rhythm or prevention of AF induction and AF recurrence.

Clovoxamine is an antidepressant and anxiolytic drug, acting as a serotonin and norepinephrine reuptake inhibitor. The drug was investigated in the double-blind clinical trials for the treatment of anxiety neurosis, where it was compared with diazepam, and found to have comparable efficacy but higher drop out rate.

Linogliride is a substituted guanidine structurally unrelated to the sulphonylureas but with a similar mechanism of action. Linogliride potentiates insulin release in isolated islets and in the perfused pancreas. In islets, linogliride is reported to stimulate insulin secretion in the presence of glucose but not in its absence. Linogliride and the sulphonylureas act via closely related mechanisms. Possible extrapancreatic effects of the agent have also been suggested. Linogliride produces hypoglycaemic effects in various non-diabetic and diabetic animals. In normal rats and dogs, it improves glucose tolerance and in fasted rats or mice, linogliride lowers blood glucose. Linogliride showed modest effects in the db/db mice but significantly lowered fasting blood glucose in neonatal streptozotocin-treated rats. Clinical studies with non-insulin-dependent diabetes patients have shown linogliride to be effective at lowering fasting and postprandial plasma glucose levels in non-insulin-dependent diabetes patients. linogliride leads to a decrease in the activity of ATP-sensitive K+ channels.

Dazopride is an antagonist of the 5-HT3 receptor and agonist of the 5-HT4 receptor, structurally related to metoclopramide. Dazopride was developed by A. H. Robins Company as an antiemetic and gastroprokinetic drug. Dazoptide demonstrated an antiemetic effect in the clinic after i.v. infusion to patients, receiving anticancer therapy.

Duoperone is a neuroleptic agent. Duoperone blocked d-amphetamine lethality in mice under aggregated conditions when the pretreatment interval was between one hour and seven days. Conditioned avoidance responding in mice and cats was suppressed by duoperone in doses that did not impair escape behavior. Duoperone produced catalepsy in rats. The onset of this effect was delayed and the duration was prolonged when compared with that of chlorpromazine. It was a potent antiemetic agent in dogs, with a delayed onset and prolonged duration of action.

Deramciclane is camphor derivative. It is an anxiolytic agent that binds with high affinity to 5-HT2A/2C receptor. Deramciclane showed significant evidence of efficacy for the treatment of generalized anxiety disorder in adult patients. A single dose of deramciclane was rapidly absorbed with peak plasma concentrations being reached after about 3 h. Deramciclane has a half-life of around 27 h. The most commonly reported adverse event was headache. In the in vitro studies deramciclane concentration-dependently inhibited NMDA evoked spreading depression.

FEZOLAMINE is a nontricyclic antidepressant. It acts as a serotonin, norepinephrine, and dopamine reuptake inhibitor, with a preference for the former neurotransmitter. It was found to be effective and well tolerated in clinical trials but was never marketed.

Tampramine (also known as AHR-9377) is a potent and selective, noncompetitive inhibitor of norepinephrine reuptake possesses antidepressant activity. This drug was studied for the treatment of the major depressive disorder; however, this study was discontinued.

Mixidine is negative chronotropic agent patented by McNeil Laboratories. Mixidine produced a dose-related decrease in heart rate elevated reflexly by aminophylline, by beta-adrenergic stimulation induced by isoproterenol, by sympathetic nerve stimulation and by intravenous infusion of glucagon. Mixidineattenuated the increase in contractile force produced by sympathetic nerve stimulation but not that induced by isoproterenol. The compound antagonized the increase in the rate of isolated guinea-pig atria induced by both isoproterenol and histamine. In the conscious dog, Mixidine caused no decrease in resting heart rate, mean arterial pressure and cardiac output. It reduced atropine-induced sinus tachycardia as well as that induced by treadmill exercise.

KETIPRAMINE, an imipramine derivative, is a tricyclic antidepressant. In clinical trials, it was found to be as effective as imipramine for the depression treatment, with fewer secondary effects.