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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wong, T. M. Walker, M. J. Pugsley, M. K. Penz, W. P. |
| Description | Author Affiliation: Pugsley MK ( Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.) |
| Abstract | 1. The cardiovascular actions of U-50,488H, a kappa-receptor agonist, were studied in rat isolated perfused hearts, and in anaesthetized rats, over concentrations or doses generally above those required to produce kappa-receptor-mediated effects. 2. U-50,488H dose-dependently decreased left-ventricular peak systolic pressure and beating rate in vitro and reduced blood pressure and heart rate in vivo. 3. Over the concentration range of 1-30 microM in vitro, and the dose-range of 0.5-32 mumol kg-1 in vivo, U-50,488H prolonged the P-R, QRS and Q-T intervals of the ECG. 4. The effects of U-50,488H were not antagonized by an opioid receptor antagonist, naloxone (1 microM or 8 mumol kg-1). Similarly, the opioid receptor antagonist, MR 2266, at 8 mumol kg-1 did not significantly reduce the cardiovascular actions of U-50,488H in vivo. 5. The actions of U-50,488H on responses to electrical stimulation were also studied. Over the dose range of 0.5-32 mumol kg-1, U-50,488H altered thresholds and effective refractory period. It had a biphasic action on thresholds for induction of ventricular fibrillation. Thresholds were decreased at lower doses (0.5-4 mumol kg-1) but increased at higher doses (8-32 mumol kg-1). The effects of lower doses were blocked by naloxone. Effective refractory period and threshold pulse width only increased with dose. 6. In conclusion, U-50,488H at high concentration, had direct depressant actions on cardiac contractility, electrical excitability and the ECG. These depressant effects were not antagonized by the opioid receptor antagonists, naloxone and MR 2266, and probably do not involve opioid receptors. Furthermore, some of the observed effects were those expected to result from sodium channel blockade. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 105 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1992-03-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Analgesics Pharmacology Hemodynamics Drug Effects Narcotic Antagonists Pyrrolidines Receptors, Opioid Physiology 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer Animals Benzomorphans Blood Pressure Electric Stimulation Electrocardiography Heart Rate In Vitro Techniques Naloxone Rats, Inbred Strains Receptors, Opioid, Kappa Refractory Period, Electrophysiological Ventricular Fibrillation Physiopathology Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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