Opipramol is typically used in the treatment of generalized anxiety disorder (GAD).[1] 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.
Opipramols sigma-1 agonizing effects likely impart potent antitussive effects, many other sigma-1 agonists (ex. codeine, hydrocodone, and dextromethorphan) are used for this purpose.
Pharmacology
Opipramol acts as a high affinitysigma receptoragonist, primarily at the σ1 subtype, but also at the σ2 subtype with somewhat lower affinity.[1] It is this property which is responsible for its therapeutic benefits against anxiety and depression.[2] Opipramol also acts as a low to moderate affinity antagonist for the D2, 5-HT2, H1, H2, and muscarinic acetylcholine receptors. H1 and H2 receptor antagonism account for its antihistamine effects, and muscarinic acetylcholine receptor antagonism is responsible for its anticholinergic properties.[1] Sigma receptors as a set of proteins located in the endoplasmic reticulum, σ1 receptors play key role in potentiating intracellular calcium mobilization thereby acting as sensor or modulator of calcium signalling. Occupancy of σ1 receptors by agonists causes translocation of the receptor from endoplasmic reticulum to peripheral areas (membranes) where the σ1 receptors and neurotransmitter release. The biphasic action initially makes prompt improvement of tension, anxiety and insomnia. Opipramol is a tranquilizer with a thymoleptic component. After sub-chronic treatment, opipramol is significantly down-regulated to σ2 but not σ1 sites.[3]
Metabolism
Opipramol is rapidly and completely absorbed by the gastrointestinal tract. Its terminal plasma half life is 6-11 hours. After single oral administration of 50 mg, the peak plasma concentration of the drug is reached after 3.3 hours and amounts to 15.6 ng/ml. After single oral administration of 100 mg the maximum plasma concentration is reached after 3 hours and amounts to 33.2 ng/ml. The bioavailability of opipramol amounts to 94%. The plasma protein binding amounts to approximately 91% and the volume distribution is approximately 10 L/kg. Opipramol is partially metabolized in liver as deshydroxy ethyl-opipramol. Metabolization occurs through CYP2D6-isoenzyme. Elimination is 70% renally and 10% unaltered. Remaining portion is eliminated through faeces.[3]
Adverse reactions
Opipramol is a well-tolerated drug. Opipramol produces less side effects as compared to SSRIs and SNRIs. Commonly reported side effects with opipramol at the beginning of treatment include fatigue, dry mouth, blocked nose, hypotension and orthostatic disregulation. Occasionally reported side effects are dizziness, tachycardia, palpitation, tremor, weight gain, abnormal ejaculation, impotence, constipation, skin rash, urticaria. Very rare side effects (<0.01%) include seizure, tremor, akathisia, dyskinesia, ataxia, polyneuropathy, hair-fall, jaundice.[3]
Contraindications
In patients with hypersensitivity to opipramol dihydrochloride or an other component of the formulation.
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