PHARMACOLOGICAL STUDIES ON DL-PIPERONYLMETHYLAMINOPROPANE

I PERIPHERAL ACTION

Abstract

Various experiments were conducted on dl-piperonyl-methylaminopropane (dl-PMAP).1) The intravenous injection of dl-PMAP in dogs caused a rise of blood pressure and a persistent rise was achieved through reserpine administration. However, such a rise was weaker than in methamphetamine. Such pressor effect was inhibited or abolished by cocaine or tolazoline. The repeated administration of dl-PMAP caused tachyphylaxis but a larger dose than methamphetamine was required. Moreover, a cross tachyphylaxis was seen between methamphetamine and dl-PMAP. In an experiment on blood pressure and ECG changes, bradycardia was definitely observed but disappeared after vagotomy or atropine administration, being mediated reflex by the vagus nerve. However, no special change was found in ECG types.2) Through intravenous administration of dl-PMAP in dogs, respiratory excitation was exhibited, probably through the carotid sinus reflex and a central excitation effect.3) dI-PMAP exerts an facilitating effect on the isolated heart of frogs and rabbits, and rabbit heart in vivo. An inhibitory effect was seen upon the use of large doses.4) A vasoconstrictive action was observed on the blood vessels of the ear of rabbits, the whole body of frogs and the paw of dogs.5) In the isolated and intact intestine of rabbits, a slight inhibition of motility was noted. These experimental results indicated a weaker effect of dl-PMAP than that of methamphetamine. Repeated administration caused a decreasing of the effect. The action of dl-PMAP is quantitatively different from that of metham hetamine in many respects but similar in outline.The mechanism of action is apparently based on the release of norepinephrine from the peripheral adrenergic nerve, the drug being useful as a mild sympathomimetic amine.