PHARMACOLOGY OF THE ADRENERGIC BLOCKING AGENT DIMETHYLPIPERIDINO ETHYL GUANIDINE

β-N-(cis-2, 6-dimethylpiperino)-ethyl-guanidine sulphate (BD-38) was synthesized in our Institute. Some pharmacological, mainly cardiovascular, actions were investigated.Blood pressure was markedly lowered by intravenous injection (iv) of 1～5 mg/kg or intraduodenal administration of 10 mg/kg in anaesthetized cats or iv 5 mg/kg in anaesthetized dogs. There was no significant alteration in the electrocardiogram.The guinea pig ileum was set up for periarterial nerve as well as for coaxial stimulation. When the periarterial nerves were stimulated the twitch induced by coaxial stimulation was diminished. BD-38 inhibited partly the twitch in response to coaxial stimulation, and the effects of periarterial nerve stimulation were then blocked remarkably. BD-38 inhibited significantly the hypertension caused by electrical stimulation of the distal end of splanchnic nerves in anaesthetized cats. In conscious cats, iv guanethidine sulphate or BD-38 (5 or 10 mg/kg) brought about relaxations of nictitating membranes of similar intensity. In conscious cats, intragastric garage of BD-38 (10 mg/kg) produced a relaxation of nictitating membrane to an extent of about twice that by guanethidine sulphate 10 mg/kg. An increase of the dosage of guanethidine sulphate to 20 mg/kg yielded a relaxation of nictitating membrane similar to that by BD-38 (10 mg/kg). This demonstrated that BD-38 was better absorbed in the gastrointestinal tract than guanethidine sulphate.The hypotension and bradycardia caused by electrical stimulation of peripheral end of cat vagus nerve was slightly blocked by BD-38, and restored in 1/2 hour. There was no much change toward AcCh actions. BD-38 also inhibited the pressor response from occlusion of common carotid artery.In the isolated heart-lung preparations of guinea pigs, the heart rate and cardiac output showed no change at a concentration of 0.25 mg/ml blood. At 2 mg/ml, the work of the heart was not inhibited. BD-38 did not influence the toxicities of digitoxin.Subacute toxicity experiments in dogs revealed no effect on the growths and liver functions.In conclusion, BD-38 manifested a prolonged hypotensive action, displayed good absorption from the alimentary tract, lacked acute sympathomimetic reaction after ivinjecton and disclosed no direct cardiao-inhibition. Hence it is worth while to put BD-38 into clinical trial.