Comparison of the effects of mianserin and its enantiomers and metabolites on a behavioral screen for antidepressant activity.
The behavioral effects of racemic mianserin, its (+) and (-) enantiomers, and its metabolites desmethylmianserin and 8-hydroxymianserin were evaluated on the differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule, a screen known to be sensitive to and specific for the antidepressant properties of drugs. Racemic mianserin produced the antidepressant-like effect (increased reinforcement rate, decreased response rate) at 5 and 10 mg/kg. The mianserin enantiomers showed the antidepressant-like effect beginning at lower doses [(+) mianserin; 0.6 mg/kg; (-) mianserin: 2.5 mg/kg]. The mianserin metabolites showed no clear dose-related effect at doses up to 10 mg/kg. It is concluded that the antidepressant-like effects of mianserin are due to the activity of the parent compound rather than to its metabolites, and that they may be primarily attributable to the (+) enantiomer. The greater potency of (+)-mianserin may be related to its higher affinity for the 5-HT2 receptor.
Hand
T H
TH
University of Chicago, Department of Pharmacological and Physiological Sciences, IL 60637.
Marek
G J
GJ
Seiden
L S
LS
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant; D003863:Depression / Q000523:psychology*; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D013237:Stereoisomerism
D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D008803:Mianserin; C029337:8-hydroxymianserin; C056517:desmethylmianserin