The antihypertensive effect of a selective central muscarinic cholinergic antagonist: N‐(4‐diethylamino‐2‐butynyl)‐succinimide

Abstract

Corarn, W.M., and H.E. Brezenoff:The antihypertensive effect of a selective central muscarinic cholinergic antagonist: N-(4-Diethylamino-2-butynyl)-succinimide. Drug Dev. Res. 3:503-516, 1983. N-(4-Diethylamino-2-butynyl)-succinimide (DKJQl), a cholinergic antagonist selective for muscarinic receptors in the central nervous system, has an antihypertensive effect in conscious spontaneously hypertensive rats (SHR) but not in normotensive Wistar-Kyoto (WKY) control rats. Intravenous doses over a range of 3.1 to 25.0 mglkg produced a dosedependent decrease in systolic blood pressure. This effect was still apparent 24 hr after drug administration, but blood pressure returned to predrug levels by 48 hr after injection of DKJ-21. In a dose-response study, the maximum antihypertensive response in a group receiving 25.0 mglkg was 43 & 8 mm Hg. Marked variability of the maximum response was observed in all age groups and with all doses. Decreases in blood pressure up to 75 mm Hg were obtained in individual animals. The magnitude of the antihypertensive effect is not age related since lo-, 15, 22-, and 36-week-old SHR responded to the same degree after injection of 25 mglkg DKJ-21. Smaller doses (50 pg) of DKJ-21 decreased blood pressure when administered into the lateral cerebral ventricle of SHR. Vascular responses to norepinephrine, acetylcholine, dimethylphenylpiperazinium, angiotensin I, and tyramine were not inhibited by i.v. injection of DKJ-21; however, the centrally mediated pressor response to physostigmine was reduced by 60%.

Crystal structure of 4,5,6,7,8,8-hexachloro-2-(3,4-dimethoxyphenethyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione [+solvent]

“…The variety of biological activities and pharmaceutical uses of compounds containing a succinimide moiety is considerable. They include activities such as antifungal (Hazra et al, 2004), anti-tubercular (Isaka et al, 2006), CNS depressant (Aeberli et al, 1976), antispasmodic (Nunes et al, 1995), cytostatic (Crider et al, 1980), analgesic (Correa et al, 1997), antibacterial (Zentz et al, 2002), anticancer (Hall et al, 1995), anorectic (Rich & Gardner, 1983), hypotensive (Coram & Brezenoff, 1983), nerve conduction blocking (Kaczorowski et al, 2008), bacteriostatic (Piper et al, 1971), anti-convulsant (Kornet et al, 1977) and muscle relaxant (Musso et al, 2003).…”

Synthesis, Molecular Docking, and Preclinical Evaluation of a New Succinimide Derivative for Cardioprotective, Hepatoprotective and Lipid-Lowering Effects

“…A characteristic feature of succinimide derivatives is the addition of a new functional group to the succinimide ring, which further alters the spectroscopic and pharmacological properties of the resulting derivatives. Succinimide is part of many active molecules that have activities, such as CNS depressant [ 30 ], analgesic [ 31 ], antitumor [ 32 ], cytostatic [ 33 ], anorectic [ 34 ], nerve conduction blocking [ 35 ], antispasmodic [ 36 ], muscle relaxant [ 37 ], hypotensive [ 38 ], antibacterial [ 39 ], antifungal [ 40 ], anticonvulsant [ 41 ], and antitubercular [ 42 ] activities. The main site of action of succinimides is calcium channels in general and T-type channels in particular, which play an important role in the regulation of blood pressure and cardiac function [ 43 , 44 ].…”