Antagonistic effects of trifluoperazine, imipramine, and chlorpromazine against acetylcholine-induced contractions in isolated rat uterus
Balais, S.Y.; Prado, W.A.; Alves-do-Prado, W.
Zhongguo Yao Li Xue Bao 18(2): 97-100
1997
ISSN/ISBN: 0253-9756 PMID: 10072955 Document Number: 481683
AIM: To examine the effects and affinity of some phenothizines (trifluoperazine, Tri and chlorpromazine, Chl) and antidepressant (imipramine, Imi) drugs on acetylcholine (ACh)-induced uterine contraction. METHODS: Isotonic contractions of rat uterine strips were recorded. ACh was administrated to induce maximal contraction before exchange of nutrient solution. ACh was added 5 nun after the testing drugs. The nutrient solution was exchanged 4 times after each agonist (ACh or other agents) to produce maximal contraction. RESULTS: Atropine (Atr, 0.029-2.9 mu-mol cntdot L-1), 4-DAMP (3.6-360 nmol cntdot L-1), pirenzepine (Pir, 0.23-23.5 mu-mol cntdot L-1), and AF-DX 116 (0.7-35.6 mu-ol cntdot L-1) competitively antagonized the muscular uterine contraction induced by ACh(0.068-36068 mu-mol cntdot L-1). The Schild plot was linear (r = 1.00). The pKB and slopes values (95 % confidence limits) were 9.28 +- 0.12 and 1.00 +- 0.10 to Atr, 9.06 +- 0.10 and 1.10 +- 0.08 to 4-DAMP, 7.03 +- 0.15 and 0.99 +- 0.12 to Pir, and 5.60 +- 0.08 and 1. 00 +- 0.19 to AF-DX 116. Tri 0.01-2 mu-mol cntdot L-1 (pK-B = 8.39 +- 0.04) and Imi 94 - 940 nmol cntdot L-1 (pK-B = 7.21 +- 0.10) produced also a competitive antagonism of the muscular uterine contraction induced by ACh ( r 1.00), but the slope was only 0.60 +- 0.03 to Tri or 0.83 +- 0.16 to Imi. CM 2.8-5.6 mu-mol cntdot L-1 produced a weak antagonism on amplitude of m contraction induced by the cholinomimetic. CONCLUSION: The muscarinic receptors on uterus behaved as m-3 subtype. Tri and Imi, but not Chl, were competitive antagonist of muscarinic receptors of uterus. Imi behaved a simple competitive antagonist at a single site on myometrium, but Tri was not a simple competitive agent at a single site.