Opipramol

Opipramol is a psychiatric medication usually described as an atypical member of the tricyclic family ^[1]. It shares the three-ring chemical backbone of the tricyclic antidepressants, but its pharmacology sets it apart: unlike standard tricyclics, it does not meaningfully inhibit the reuptake of serotonin or noradrenaline, and its effects are instead attributed largely to its high affinity for sigma receptors ^[1][2]. For this reason it is often grouped with the anxiolytics rather than the conventional antidepressants.

The compound was developed by the Swiss company Geigy and introduced into clinical use in the early 1960s ^[1]. It has long been used in German-speaking Europe and other countries, where it is marketed under names including Insidon, and it remains in use there today. It has not been widely adopted in North America ^[1].

Opipramol is used mainly to treat generalized anxiety disorder and somatoform disorders, conditions in which anxiety and bodily symptoms without a clear physical cause are prominent ^[1][3]. A placebo-controlled clinical trial in patients with generalized anxiety disorder found opipramol to be more effective than placebo and comparable to the benzodiazepine alprazolam, while a distinctive feature of its clinical profile is a relatively prompt calming and sleep-improving effect followed by a later lift in mood ^[3]. Continued interest in sigma receptors as targets for anxiety and depression has kept opipramol relevant in discussions of that receptor system ^[2].

Opipramol is a prescription medicine dispensed as tablets and is available as a generic in the countries where it is sold ^[1]. It is generally regarded as well tolerated, and unlike drugs that act through the serotonin or noradrenaline transporters, it does not typically carry the same activation or sexual side effects; common complaints instead include tiredness, dry mouth, and low blood pressure on standing, reflecting its blockade of histamine and other receptors ^[1]. As with related compounds, monitoring is advised during longer treatment because of rare effects on the liver and blood counts.

As a dibenzazepine (tricyclic-related) agent, opipramol commonly causes sedation, dizziness, dry mouth, constipation, blurred vision, urinary retention, and weight gain, reflecting its anticholinergic and antihistaminic actions. Like other tricyclic compounds it can slow cardiac conduction and prolong the QT interval, with a rare risk of ventricular arrhythmia such as Torsades de Pointes, especially in overdose or with electrolyte imbalance. It can also lower the seizure threshold. Contraindications include untreated narrow-angle glaucoma, acute urinary retention, recent myocardial infarction, severe hepatic or renal impairment, and acute intoxication with alcohol or CNS depressants; combining it with other QT-prolonging drugs compounds cardiac risk.