Neuropharmacology of the anxiolytic drug opipramol, a sigma site ligand.
Although opipramol is structurally related to imipramine, it does not represent a tricyclic antidepressant drug as it does not inhibit the neuronal uptake of norepinephrine and/or serotonin. Unlike imipramine it is a rather potent sigma ligand with modest subclass selectivity which is similar in vitro as well as ex vivo. Opipramol is active in several behavioural paradigms indicative of anxiolytic properties at doses (1-10 mg/kg), which are also needed to occupy sigma binding sites. Somewhat higher doses (10-20 mg/kg) are needed for "antidepressant like" effects. The data allow the conclusion that interaction with sigma sites is involved in the anxiolytic and antidepressant effects of opipramol albeit a contribution of its weaker D (2)-antagonistic and 5-HT2-antagonistic properties cannot be totally be excluded.
Müller
W E
WE
Department of Pharmacology, Biocenter University Frankfurt, Marie-Curie-Strasse 9, D-60439 Frankfurt, Germany. pharmacolnat@em.uni-frankfurt.de
Siebert
B
B
Holoubek
G
G
Gentsch
C
C
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005334:Fever / Q000188:drug therapy / Q000209:etiology; D006168:Guinea Pigs; D007099:Imipramine / Q000494:pharmacology; D007103:Immobilization / Q000379:methods; D020128:Inhibitory Concentration 50; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009888:Opipramol / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017480:Receptors, sigma / Q000819:agonists* / Q000378:metabolism; D013312:Stress, Physiological / Q000150:complications / Q000188:drug therapy; D013550:Swimming
D014151:Anti-Anxiety Agents; D000929:Antidepressive Agents, Tricyclic; D017480:Receptors, sigma; D009888:Opipramol; D007099:Imipramine