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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Roberts, F. Stephenson, R. P. |
| Abstract | 1 The kinetics of action of some competitive muscarinic and histamine antagonists were examined on guinea-pig isolated ileum and their behaviour compared with the predictions of the interaction-limited model described by Paton (1961). 2 The kinetics of antagonism were not consistent with the predictions of this model: (1) The apparent dissociation rate constant calculated from the decrease in occupancy on washout was not independent of the concentration of antagonist. (2) The dissociation rate constant of a 'slow' antagonist calculated from the change in occupancy when a 'fast' antagonist was superimposed varied with the concentration of fast antagonist. (3) If the concentration of slow antagonist was increased when the fast antagonist was superimposed so that the equilibrium occupancy of the 'slow' was the same as before, a transitional phase was observed. 3 The kinetics of antagonism were observed in longitudinal muscle strips and intact pieces of ileum, bathed in Tyrode or Krebs solution, and with isometric and isotonic recording. No evidence was found that the discrepancies between the interaction-limited model and the observed kinetics could be accounted for by the experimental method used. 4 It is therefore concluded that either access is rate-limiting in these circumstances or, if interaction is rate-limiting, some alternative interaction-limited model is required to describe the kinetics of antagonism. In either case it would seem unwise at this time to calculate antagonist-receptor rate constants from the observed kinetics of antagonism. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 1 |
| Volume Number | 58 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1976-09-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Ileum Drug Effects Muscle Contraction Animals Antazoline Pharmacology Atropine Benzilates Drug Interactions Guinea Pigs In Vitro Techniques Kinetics Pyrilamine Quaternary Ammonium Compounds Tropanes |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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