| Abstract: | N-(4-Diethylamino-2-butynyl)-succinimide (DKJ-21), 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 mg/kg produced a dose-dependent 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 mg/kg 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 10-, 15-, 22-, and 36-week-old SHR responded to the same degree after injection of 25 mg/kg DKJ-21. Smaller doses (50 μg) 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%. |
