Abstract |
1. A series of substituted tetrahydroisoquinolins derived from the cleavage products of tetrandrine were found to inhibit [3H]- nitrendipine binding to rat cerebral cortical membranes. Those compounds which displaced [3H]- nitrendipine binding were also able to inhibit high KCl-induced contraction of rat aorta in vitro. 2. There was a significant correlation between the ability of these tetrahydroisoquinolines to inhibit [3H]- nitrendipine binding and KCl-induced contraction (r = 0.99, P less than 0.001). 3. CPU-23 (1-(1-[(6-methoxy)-naphth-2-yl])-propyl-2-(1- piperidine)-acetyl- 6,7- dimethoxy-1,2,3,4- tetrahydroisoquinoline), one of the most potent compounds identified in this series, behaved as a simple competitive inhibitor at the [3H]- nitrendipine binding site and reduced the apparent affinity but not the maximal number of binding sites in saturation analysis. 4. In contrast to nifedipine which caused hypotension and tachycardia, CPU-23 induced both hypotension and bradycardia in a dose-dependent manner in pentobarbitone-anaesthetized Sprague-Dawley rats, spontaneously hypertensive and age-matched normotensive WKY rats. 5. It is suggested that CPU-23 may exert its cardiovascular effects via interaction with the dihydropyridine binding site on the L-type calcium channel.
|
Authors | H Dong, C M Lee, W L Huang, S X Peng |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 107
Issue 1
Pg. 262-8
(Sep 1992)
ISSN: 0007-1188 [Print] England |
PMID | 1330162
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Alkaloids
- Benzylisoquinolines
- Calcium Channels
- Isoquinolines
- Piperidines
- Tetrahydroisoquinolines
- CPU 23
- tetrandrine
- Potassium Chloride
- Nitrendipine
|
Topics |
- Alkaloids
(metabolism, pharmacology)
- Animals
- Aorta
- Benzylisoquinolines
- Blood Pressure
(drug effects)
- Calcium Channels
(drug effects)
- Cerebral Cortex
(drug effects, metabolism)
- Dose-Response Relationship, Drug
- Female
- Heart Rate
(drug effects)
- Hypertension
(physiopathology)
- Isoquinolines
(metabolism, pharmacology)
- Male
- Nitrendipine
(metabolism)
- Piperidines
(metabolism, pharmacology)
- Potassium Chloride
(pharmacology)
- Rats
- Rats, Inbred SHR
- Rats, Sprague-Dawley
- Rats, Wistar
- Tetrahydroisoquinolines
- Vasoconstriction
(drug effects)
|