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THE FACTORS INFLUENCING THE TIME COURSE OF DRUG ACTION AT α‐ADRENOCEPTORS: AN INVESTIGATION OF THE EFFECTS OF CLONIDINE IN THE PITHED RAT
Author(s) -
DOCHERTY J.R.,
McGRATH J.C.
Publication year - 1980
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1980.tb10411.x
Subject(s) - clonidine , endocrinology , medicine , agonist , chemistry , isometric exercise , blood pressure , receptor
1 The time courses of the pre‐ and post‐junctional effects of clonidine were examined on heart rate and blood pressure and on the isometric tension responses of the vas deferens and anococcygeus in situ in the pithed rat. Plasma levels of clonidine were also monitored. 2 The time courses of the pre‐junctional inhibition of sympathetic nerve mediated responses in all tissues monitored were related to the plasma levels of clonidine, but the degree of inhibition which was observed varied with the tissue and with the test stimulus employed. 3 The post‐junctional agonist effects of clonidine, especially at low doses, exhibited an initial ‘peak’ followed by a decline to a lower plateau. This decline of the response was not due to receptor desensitization but was related to a decline in the plasma clonidine level from an initially high value caused by injection of a bolus. 4 The factors determining the time course of drugs' effects in the preparation are discussed and it is concluded that pre‐ and post‐junctional responses should be compared at a point in time after injection of the drug, at which equilibration has occurred.