Nicotinic-like effects and tissue disposition of isopropylamine

Previous studies in our laboratory have demonstrated that the acute sympathomimetic effects of isopropylamine are due to stimulation of autonomic ganglia. The present studies were designed to determine whether isopropylamine produced ganglionic blockade after its initial stimulation of autonomic ganglia. Infusion of isopropylamine (2.5 mg/kg/min) produced an initial increase in arterial pressure and heart rate which was followed by a prolonged hypotension and bradycardia; lower doses produced only a hypotensive response. After infusion of isopropylamine, the positive chronotropic responses to preganglionic cardioaccelerator nerve stimulation were significantly reduced, whereas the responses to postganglionic nerve stimulation were essentially unchanged. Similarly, the negative chronotropic responses to peripheral vagal stimulation were significantly reduced after isopropylamine administration. Moreover, isopropylamine reduced the cardiovascular responses to i.v. injections of the ganglion nicotinic stimulant, dimethylphenylpiperazinium iodide. Studies on the disposition of isopropylamine indicated that there was significant cumulation of isopropylamine in all tissues as compared to plasma. When the relationship between plasma isopropylamine and the decreases in mean arterial pressure was examined, a significant positive correlation (r = 0.87) was found. These results indicate that isopropylamine has both ganglion stimulating and blocking properties and is similar in its action to the classical nicotinic ganglion stimulant drugs such as dimethylphenylpiperazinium iodide and tetramethylammonium.