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ApprovedFDA approvedModerate evidence

Opipramol

Atypical tricyclic and sigma receptor ligand: a prescription anxiolytic without dependence.

AnxiolyticAtypical tricyclicAnxiolyticMoodnoo.affects.sigmanoo.affects.histamineSerotonin

Pharmacology

ClassAnxiolytic · Mood
Primary targetSigma receptor ligand + H1 antagonist
Targets3 receptor targets
Half-lifeAbout 6-11 hours (suitable for once-daily evening dosing)
OnsetSedation appears within hours; the full anxiolytic effect builds over 1-3 weeks
EvidenceModerate evidence
Affected systemsnoo.affects.sigmanoo.affects.histamineSerotonin

Contents

WHAT IS OPIPRAMOL?

Detailed overview

Opipramol is an atypical tricyclic compound that, unlike classical tricyclic antidepressants, does not inhibit monoamine reuptake; instead it acts primarily as a ligand at sigma-1 and sigma-2 receptors and as an antagonist of histamine H1 receptors. In Europe (e.g. Germany, Poland) it is an approved prescription medicine for generalized anxiety disorder (GAD) and somatoform disorders. In placebo-controlled trials its anxiolytic effect was comparable to alprazolam but without the dependence and tolerance typical of benzodiazepines. It is not FDA-approved and is not marketed in the United States.

Mechanism

Sigma-1/2 ligand + H1 antagonist

Half-life

About 11 hours (once-daily dosing)

Legal status

Prescription medicine (EU), not in US

Receptor profile

  • Sigma-1 / sigma-2 receptorsStrong
  • Histamine H1 receptorStrong
  • D2 / 5-HT2 receptors (weak)Weak

Safety

Side effects, stop signs, contraindications

Side effects · 5

  • Tiredness and drowsiness, especially in the first days of treatment (H1 blockade)
  • Dry mouth and other mild anticholinergic-type effects
  • Orthostatic hypotension: dizziness or lightheadedness on standing
  • Weight gain and increased appetite with longer use
  • Rare liver function and blood count changes, so periodic monitoring is advised

Contraindications · 5

  • Acute intoxication with alcohol, hypnotics, analgesics or psychotropic drugs
  • Urinary retention, narrow-angle glaucoma, severe prostate enlargement (anticholinergic effect)
  • Should not be combined with MAO inhibitors or given immediately after stopping them
  • Severe liver or kidney impairment and known QT prolongation require increased caution
  • Pregnancy and breastfeeding: only under a clear medical indication after risk-benefit assessment

Related Nootropics

Same therapeutic category

Studies

Related research and clinical findings

FAQ

FAQ

Atypical tricyclic and sigma receptor ligand: a prescription anxiolytic without dependence.

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Structure & chemistry

TypeAnxiolytic
FormulaC23H29N3O
UpdatedJuly 10, 2026
MolekulaX Editorial Team·Source-verified · PubMed · FDA · EMA
Updated: July 10, 2026

The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.