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PubMed1985

A comparison of cardiovascular and smooth muscle effects of 5-hydroxytryptamine and 5-carboxamidotryptamine, a selective agonist of 5-HT1 receptors.

The pharmacological effects of 5-hydroxytryptamine (5-HT) on heart rate, arterial blood pressure and urinary bladder pressure in the rat, and on the bronchi and ileum of the guinea-pig were compared with those of 5-carboxamidotryptamine (5-CT), a compound which binds specifically and with high affinity to 5-HT1 binding sites in rat brain membranes. 5-HT caused a transient bradycardia and a triphasic blood pressure response consisting of an initial short-lasting hypotensive, a pressor and, finally, a longer-lasting depressor phase. Analysis with mecamylamine, cyproheptadine and ketanserin indicated that the initial bradycardia and hypotension, and the pressor and tachycardic responses to 5-HT were due to, respectively, the M and 5-HT2 receptors. 5-CT showed no or little activity on these receptors, but elicited a marked hypotensive response. The prolonged hypotensive effects of both 5-HT and 5-CT were apparently mediated by 5-HT1 receptors, since they were unaffected by cyproheptadine or ketanserin, but were antagonized by high doses (greater than 2.5 mg.kg-1) of methysergide, which has an appreciable affinity for 5-HT1 binding sites. On the guinea-pig bronchi and the rat urinary bladder, which were contracted by 5-HT via 5-HT2- and, in the case of bladder, also via M-type 5-HT receptors; 5-CT was without any effect. The guinea-pig isolated ileum was relaxed by low concentration (5 X 10(-6) M), probably via 5-HT1 receptors demonstrated in this tissue, and contracted by higher concentrations of 5-CT. However, the contractile effect of 5-HT on the ileum, exerted via the M- and 5-HT2-type 5-HT receptors, was much more than that of 5-CT. Our results demonstrate that 5-CT not only has a binding, but also a functional specificity for 5-HT1 receptors. This compound seems to be a useful tool for investigating 5-HT1 receptor mediated functional responses.

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