SOME PHARMACOLOGICAL ACTIONS OF METHYL- SUBSTITUTED PIPERIDINO ETHYLGUANIDINES

Three derivatives of piperidino ethyl guanidine sulphate (P) were synthesized by Bai et al in our Instituter: β-N-(2,2,6,6-tetramethylpiperidino)-ethyl-guanidine sulphate (BD-31), β-N-(2-methylpiperidino)-ethyl-guanidine sulphate (BD-37), and β-N-(cis-2,6-dimethylpiperidino)-ethyl-guanidine sulphate (BD-38). Their pharmacological actions were compared with guanethidine sulphate (G).The acute intraperitoneal LD₅₀ in mice of P, BD-37, BD-38, G and BD-31 were 367, 243, 202, 155 and 78 mg/kg, respectively. Intravenous injections of P, BD-37 and G in anaesthetized rats and cats brought about a transient lowering of blood pressure, followed by a rise and then a gradual decline, whereas BD-31 and BD-38 produced only a hypotension. For the hypotensive potency: BD-38 and BD-31>BD-37 and G>P. P, BD-37, BD-31 and G inhibited the hypertensive effect of tyramine. BD-37, BD-38 and G sensitized, but BD-31 inhibited slightly, the hypertensive effect of noradrenaline. P, BD-37 and G markedly augmented the contraction of guinea pig auricles, though BD-31 and BD-38 were devoid of this action. Experiments on cat sympathetic nerve and isolated guinea pig vas deferens showed that BD-31 blocked moderately the Sympathetic ganglion and blocked mildly the sympathetic nerve endings; BD-37 and BD-38 blocked sympathetic nerve endings to an extent simiiar to hatby G; P blocked slightly only the vas deferens preparation. P, BD-37, BD-38 and G decreased, but BD-31 did not decrease, the noradrenaline contents in the rat heart.En résumé: BD-38 selectively blocked the sympathetic nerve endings, lacked the sympathomimetic action of G, and possessed a considerable hypotensive action.