Relaxant Action of Azulene‐1‐carboxamidine Derivative N1, N1‐dimethyl‐N2‐(2‐pyridylmethyl)‐5‐isopropyl‐3,8‐dimethylazulene‐1‐carboxamidine (HNS‐32) in Pig Coronary Artery

Abstract

HNS-32 (N1N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3,8-dimethylazulene-1-carbox-amidine) (CAS 186086-10-2) is a newly synthesized compound with an azulene structure within the molecule. The coronary relaxant action of HNS-32 was investigated pharmaco-mechanically on isolated pig coronary artery. The effects of HNS-32 were compared with diltiazem, a Ca2+-channel blocker. HNS-32 inhibited sustained contractions evoked by high KCl, prostaglandin F2α, a thromboxane A2 mimetic (U46619) and endothelin-1 in a concentration-dependent manner. The potency of HNS-32 to inhibit these contractions was 5- to 40-times lower than diltiazem. HNS-32 also diminished phasic contractions induced by acetylcholine, histamine and 5-hydroxytryptamine. Addition of excess Ca2+ counteracted HNS-32-induced inhibition of high KCl-induced contraction only by approximately 10% whereas it restored diltiazem-induced inhibition by about 50%. Suppression of the contractile response to a phorbol ester (phorbol 12,13-dibutyrate) by HNS-32 was approximately 40%. HNS-32 prevents coronary contractions produced by a wide variety of spasmogens. Although inhibitions of L-type Ca2+ channels and protein kinase C may be partly responsible for HNS-32 action, some direct action on the contractile systems seems to be involved in the coronary relaxation by HNS-32.