[Quinolozidinylalkylamines with antihypertensive activity].
Since lupinylamine [(I); R = H] exhibits hypotensive activity, mainly due to ganglionic blocking properties, and it is known that a high degree of steric hindrance around the basic function of other ganglioplegic amines is of paramount importance for optimal activity, several guinolizidine derivatives were prepared. They differ in the length of the alkyl chain connected to the ring and in the position of the amino group along the chain. Some N-substituted derivatives of 2-quinolizidin-1'alpha-yl-ethylamine (II) together with O-lupinylhydroxylamine and 2-quinolizidin-1'beta-yl-ethylamine, respectively isosteric and epimeric to it, were also prepared. When administered orally to spontaneously hypertensive rats, the amines (II), (III) and (XI) produced high and long-lasting antihypertensive activity, while the remaining compounds so far tested were inactive or had only modest effect on blood pressure. Compared with alpha-methyl-DOPA, amine (II) appears to be approximately two to three times as potent. The antihypertensive activity of (II) appears to be linked to glanglionic blocking properties, since this amine proved 1,2 times as potent as mecamylamine in the inhibition of cat nictitating membrane response to stimulation of the preganglionic sympathetic nerve.
D000588:Amines / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004353:Drug Evaluation, Preclinical; D006339:Heart Rate / Q000187:drug effects; D009541:Nictitating Membrane / Q000187:drug effects; D011807:Quinolizines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
D000588:Amines; D000959:Antihypertensive Agents; D011807:Quinolizines
Chinolizidinilalchilammine ad azione antiipertensiva.