Inhibition of vasoconstriction by AJ‐2615, a novel calcium antagonist with α₁‐adrenergic receptor blocking activity in human conduit arteries used as bypass grafts

Q2 · MEDICINE

Article

Author: Floten, Storm H. ; He, Guo-Wei ; Liu, Ming-Hui ; Yang, Qin

Aims Graft spasm may develop during coronary artery bypass grafting and reversal of spasm is still challenging. The purpose of this study was to investigate the in vitro vascular relaxant properties of AJ‐2615 in human internal mammary artery (IMA).Methods We studied 264 IMA rings taken from 65 patients undergoing coronary artery bypass grafting surgery with organ bath technique. The interaction between AJ‐2615 and various vasoconstrictors was investigated in two ways.Results AJ‐2615 caused complete relaxation in methoxamine‐contracted IMA rings (100.0±0.0%; n = 8) and nearly full relaxation in potassium chloride‐contracted IMA rings (91.4±5.7%; n = 8) or noradrenaline‐contracted IMA rings (89.3±2.8%; n = 8). AJ‐2615 also induced remarkable relaxation in IMA rings contracted by other vasoconstrictors. In comparison with the α1‐adrenoceptor antagonist prazosin, AJ 2615 showed similar maximal relaxation in IMA rings contracted by methoxamine or norepinephrine. On the other hand, incubation with AJ‐2615 (0.1–1 µm) significantly inhibited all the vasoconstrictor‐mediated vasoconstriction except endothelin‐1 in a concentration‐dependent manner.Conclusions The results suggested that in human IMA, AJ‐2615 has an inhibitory effect on vasoconstriction mediated by a variety of vasoconstrictors and the mechanism of relaxation may be related to its calcium antagonism and α1‐adrenergic receptor blocking activity. AJ‐2615 may have important clinical implications for patients undergoing coronary artery bypass surgery for reversing and preventing graft spasm.

01 Jan 1999·Clinical and Experimental HypertensionQ4 · MEDICINE

New Classes of Antihypertensive Drugs: Therapeutic Potentials

Q4 · MEDICINE

Review

Author: R. K. Goyal ; N. K. Singh

A number of new classes of antihypertensive drugs have become available in the recent years which appear to hold therapeutic potential for better management of hypertension. Losartan, an angiotensin II receptor antagonist, does not produce cough which is classically seen with ACE inhibitors. Fenoldopam, a dopamine D1-receptor agonist, has a rapid and short duration of action and is ideally suited by intravenous infusion for quick control of BP in hypertensive emergencies. Kentaserin, a serotonin (5-HT2A) receptor antagonist, has a long duration of action and can be given once daily. It has the added benefit of having antiplatelet effect. Monatepil, a dual alpha-receptor and calcium channel blocker, has potent antihypertensive effect, lowers serum cholesterol and also has antiatherosclerotic effect. Dual ACE and endopeptidase inhibitor, such as alatriopril, has a "broad spectrum" antihypertensive effect and may be effective in majority of hypertensive patients. Many other classes of antihypertensive drugs are still in the investigative stage, and their therapeutic potentials and safety need to be ascertained in long-term controlled clinical trials.

01 Jan 1998·Japanese Journal of Pharmacology

Effects of Monatepil Maleate, a New Ca2+ Channel Antagonist With α1-Adrenoceptor Antagonistic Activity, on Cholesterol Absorption and Catabolism in High Cholesterol Diet-Fed Rabbits

Article

Author: Fujitani, Buichi ; Minato, Hisao ; Ikeno, Akihisa ; Sumiya, Toshiki ; Masuda, Yoshinobu ; Kurono, Masuo ; Yasuba, Masashi ; Hosoki, Kanoo

The mechanism of the prophylactic effect against hyperlipidemia by monatepil maleate was investigated in animal models. Monatepil maleate is an antihypertensive agent with Ca2+-channel antagonistic, alpha1-adrenergic receptor-blocking, and lipid peroxidation inhibitory activity. In high cholesterol diet-fed rabbits, monatepil maleate (30 mg/kg, p.o., once daily for 9 weeks) showed a prophylactic effect against increases in total cholesterol and beta-lipoprotein. Monatepil maleate significantly accelerated the clearance of radioactivity from the blood after intravenous injection of low-density lipoprotein (LDL) labeled with [1alpha,2alpha (n)-3H]cholesterol, increasing biliary excretion of [3H]-bile acids without modifying bile acid composition. Furthermore, monatepil maleate tended to inhibit the absorption of orally administered [1alpha,2alpha (n)-3H]cholesterol from the gastrointestinal tract in these rabbits. In Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of hepatic LDL receptor deficiency, monatepil maleate (30 mg/kg, p.o., once daily for 6 months) did not suppress the increase in plasma lipids. These results suggest that the plasma lipid lowering effect of monatepil maleate requires the presence of hepatic LDL receptors. It is also suggested that monatepil maleate improves plasma lipid metabolism through two mechanisms: enhancement of clearance of plasma LDL, which may be mediated by up-regulation of hepatic LDL receptors, and acceleration of conversion of free cholesterol to bile acids in the liver.

100 Deals associated with Monatepil maleate

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KEGG	Wiki	ATC	Drug Bank
D01171	Monatepil maleate	-	-

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Angina Pectoris	NDA/BLA	JP	Dainippon Pharmaceutical Co., Ltd.	-
Angina Pectoris	NDA/BLA	-	Sumitomo Pharma Co., Ltd.	-
Arrhythmias, Cardiac	NDA/BLA	JP	Dainippon Pharmaceutical Co., Ltd.	-
Atherosclerosis	NDA/BLA	JP	Dainippon Pharmaceutical Co., Ltd.	-
Hypertension	NDA/BLA	-	Sumitomo Pharma Co., Ltd.	-
Hypertension	NDA/BLA	JP	Dainippon Pharmaceutical Co., Ltd.	-

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