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Colpaert FC. 
“In Vivo Evidence Of Mixed Agonist/antagonist Activity Exerted By The Purported 5-hydroxytryptamine Antagonists Mianserin, Methysergide, And Cyproheptadine: A Drug Discrimination Analysis”. 
Progress in Neuro-Psychopharmacology. 1980;? (Suppl. 1).
Abstract
This study preasnts a drug discrimination analysis of the in vivo antagonist and agonist activity exerted by purported 5-hydroxytryptamine (5-HT) antagonists. Rats were trained to discriminate 0.16 mg/kg lysergic acid diethylamide (LSD) from saline as described previously (Europ.J. Pharmacol. 58, 505-509, 1979). The purported antagonists were administered (B. C. injections, t-0 min) in combination with either saline or 0.16 mg/kg LSD (i. p. injections, t-15 min) The data indicate that mianserin (2.5 - 40 mg/kg), methysergide (0. 63 - 40 mg/kg), and cyproheptadine (0. 04 - 10 mg/kg) induce partial or complete generalization with LSD; the dose-response curves were relatively flat, and reached maximum effects of 86 %, 86 %, and 57 % respectively. Using the same injection parameters, mianaerin (0. 01 - 2.5 mg/kg), methysergide (2. 5 mg/kg), and cyproheptadine (0. 04 - 0.63 mg/kg) also produced a paradoxical antagonism of LSD; the dose-response curves had an inverted U-shape, and reached maximum effects of 57 %, 14 % and 43 % respectively. These data are evidence that mianserin, methysergide, and cyproheptadine exert mixed agonist-antagoniat activity at LSD-sensitive 5-HT-receptor sites in the rat central nervous system.
Notes # : 12th Congress of the Collegium Internationale NeuroPharmacologicum (CINP), Göteborg (S), Jun 22-6, 1980. Pergamon Press, Oxford, New York etc., 180, p. 110, Abstr. No. 130
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