Opipramol (Synonyms: G-33040, GR-33040, NSC 169867)

Opipramol is a sigma-1 (σ1) and σ2 receptor ligand.1 It binds to σ1 and σ2 receptors in guinea pig brain membrane preparations (IC50s = 7 and 56 nM, respectively). It is selective for σ1 and σ2 over histamine H2, dopamine D1, α1- and α2-adrenergic, and muscarinic M1 receptors (IC50s = 4,300, 900, 200, 6,100, and 3,300 nM, respectively) and has no effect on serotonin (5-HT) or norepinephrine uptake (IC50s = >10,000 nM for both), but does bind to histamine H1 and dopamine D2 receptors (IC50s = 12 and 120 nM, respectively), as well as the 5-HT receptor subtype 5-HT2 (IC50 = 120 nM). Opipramol (0.01 mg/kg) increases social interaction time in a social exploration test in rats, indicating anxiolytic-like activity. It also decreases immobility time in the forced swim test in rats, indicating antidepressant-like activity, when administered at a dose of 10 mg/kg.

|1. MÜller, W.E., Siebert, B., Holoubek, G., et al. Neuropharmacology of the anxiolytic drug opipramol, a sigma site ligand. Pharmacopsychiatry 37(Suppl 3), S189-S197 (2004).