Opipramol

Opipramol, sold under the brand name Insidon among others, is an anxiolytic and antidepressant which is used throughout Europe. Although it is a member of the tricyclic antidepressants (TCAs), opipramol is atypical among TCAs and its primary mechanism of action is much different in comparison. Most TCAs act as monoamine reuptake inhibitors, but opipramol does not, and instead acts primarily as a sigma receptor agonist. It is a dibenzazepine (iminostilbene) derivative. Opipramol was developed by Schindler and Blattner in 1961. Opipramol, sold under the brand name Insidon among others, is an anxiolytic and antidepressant which is used throughout Europe. Although it is a member of the tricyclic antidepressants (TCAs), opipramol is atypical among TCAs and its primary mechanism of action is much different in comparison. Most TCAs act as monoamine reuptake inhibitors, but opipramol does not, and instead acts primarily as a sigma receptor agonist. It is a dibenzazepine (iminostilbene) derivative. Opipramol was developed by Schindler and Blattner in 1961. Opipramol is typically used in the treatment of generalized anxiety disorder (GAD) and somatoform disorders. Its anxiolysis becomes prominent after only one to two weeks of chronic administration. Upon first commencing treatment, opipramol is rather sedating in nature due to its antihistamine properties, but this effect becomes less prominent with time. Experimental animal studies did not indicate injurious effects of opipramol on the embryonic development or fertility. Opipramol should only be prescribed during pregnancy, particularly in the first trimester, for compelling indication.It should not be used during lactation and breastfeeding, since it passes into breast milk in small quantities. The frequently (≥1% to <10%) reported adverse reactions with opipramol especially at the beginning of the treatment include fatigue, dry mouth, blocked nose, hypotension, and orthostatic dysregulation. The adverse reactions reported occasionally(≥0.1% to <1%) include dizziness, stupor, micturition disturbances, accommodation disturbances, tremor, weight gain, thirst, allergic skin reactions (rash, urticaria), abnormal ejaculation, erectile impotence, constipation, transient increases in liver enzyme activities, tachycardia, and palpitations. Rarely (≥0.01% to <0.1%) reported adverse reaction includes excitation, headache, paresthesia especially in elderly patients, restlessness, sweating, sleep disturbances, edema, galactorrhea, urine blockage, nausea and vomiting, collapse conditions, stimulation conducting disturbances, intensification of present heart insufficiency, blood profile changes particularly leukopenia, confusion, delirium, stomach complaints, taste disturbance, and paralytic ileus especially with sudden discontinuation of a longer-term high-dose therapy. Very rarely (<0.01%) adverse reaction includes seizures, motor disorder, (akathisia, dyskinesia), ataxia, polyneuropathy, glaucoma, anxiety, hair loss, agranulocytosis, severe liver dysfunction after long-term treatment, jaundice, and chronic liver damage. Symptoms of intoxication from overdose include drowsiness, insomnia, stupor, agitation, coma, transient confusion, increased anxiety, ataxia, convulsions, oliguria, anuria, tachycardia or bradycardia, arrhythmia, AV block, hypotension, shock, respiratory depression, and, rarely, cardiac arrest. As therapy of intoxication, specific antidote is not available, removal of the drug by vomiting or gastric lavage should be done. Continuous cardiovascular monitoring for at least 48 hours should be done. In case of respiratory failure due to overdose, intubation and artificial respiration should be done. During severe hypotension due to overdose, corresponding recumbent positioning, plasma expander, dopamine or dobutamine as drops-infusion should be initiated. In heart rhythm disturbances, individualized treatment should be done where appropriate pacemaker and compensation in low potassium levels and possible acidosis should be done. While in convulsions due to overdose, administration of intravenous diazepam or another anticonvulsant agent such as phenobarbital or paraldehyde should be done though intensification of existing respiratory insufficiency, hypotension, or coma may happen.