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Connell DJ, Middlemiss DN, Stone MA.
“Further evidence for an interaction of propranolol with the central 5-hydroxytryptamine (5-HT) receptor”.
Brit.J.Pharmacol.. 1980;68(1):173P-174P.
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Abstract
The interaction of beta-adrenoceptor antagonists with the [3H]-LSD receptor was investigated. Synaptic membranes from whole rat brain (minus the cerebellum) were prepared and binding studies carried out as previously described. Tritiated ligand concentrations were: [3H]-5-HT (5 nM); [3H]-dihydroalprenolol (DHA I nM) and t3H3-LSD (2 nM). Non specific binding was defined as the radioligand bound in the presence of a large excess of cold drug: 5-HT (1 mcM), (-)-propranolol (0.1 mcM) and LSD (1 mcM), respectively. Compounds studied were oxprenolol, alprenolol, (-)-propranolol, (+)-propranolol. practolol, 5-HT, tryptamine, 5-methoxytryptamine. LSD, cinanserin, methiothepin, mianserin, cyproheptadine, methysergide. 5-methoxy-N,N-dimethyltryptamine and 5-hydroxy-N,N-dimethyltryptamine. The displacement of [3H]-LSD was, as has previously been shown for the displacement of [3H]-5-HT, stereospecific with being more potent than (+)-propranolol. The potency of § adrenoceptor antagonists against [3H]-5-HT binding was equal to or greater than their potency against [3H]-LSD binding. Classical 5-HT antagonists had a considerably greater affinity for [3H]-LSD binding sites. In order to demonstrate that the interaction with the 5-HT receptor may occur in vivo, propranolol was administered to rats, and 1 hr later a standard synaptosomal preparation made. (-)-Propranolol (10 mg/kg i.p.) but not (+)-propranolol (40 mg/kg i.p.) caused an apparent reduction in the number of t3H]-5-HT receptors. Similar results were obtained with (-)-propranolol (3 mg/kg i.p.) against the [3H]-DHA receptor. (+)-Propranolol was inactive at 10 mg/kg i.p. These results lend support to the hypothesis that propranolol may be a central 5-HT antagonist in animals.
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