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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Matu, K. Mitchell, P. D. Ince, F. Smith, G. W. Naya, I. Farmer, J. B. Springthorpe, B. |
| Description | Author Affiliation: Smith GW ( Fisons plc, Department of Pharmacology, Loughborough, Leicestershire.) |
| Abstract | 1. FPL 63012AR is a D1-receptor agonist in the dog kidney, 10 times as potent as dopamine, reducing renal vascular resistance by 20% with an intra-arterial dose of 0.42 nmol kg-1. 2. No prejunctional inhibitory D2-receptor agonist activity was detected in either the isolated ear artery of the rabbit or in the conscious dog as D2-receptor-mediated emesis. 3. Unlike dopamine, FPL 63012AR had no significant agonist activity at alpha 1-, alpha 2-, beta 1- or beta 2-adrenoceptors. 4. FPL 63012AR is a potent inhibitor of [3H]-noradrenaline uptake (Uptake1) into brain synaptosomes, with an IC50 of 29.5 nM, i.e. 9.2 times more potent than dopamine. 5. The ability to block Uptake1, in the anaesthetised dog was confirmed by inhibition of the tyramine-induced pressor and inotropic responses. 6. Intravenous infusion of FPL 63012AR in anaesthetized and conscious dogs (0.3 to 3 nmol kg-1 min-1) reduced vascular resistance and increased blood flow to the kidney which was accompanied by hypotension and tachycardia. 7. It is concluded that FPL 63012AR is an example of a novel class of potent agonists at the D-receptor. Such compounds may have the potential for use clinically in improving renal perfusion and reducing afterload. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 100 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1990-06-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Catecholamines Pharmacology Dopamine Agents Receptors, Dopamine Drug Effects Anesthesia Animals Benzazepines Guinea Pigs Heart Rate Hemodynamics In Vitro Techniques Muscle, Smooth, Vascular Myocardial Contraction Papillary Muscles Rabbits Receptors, Adrenergic, Alpha Receptors, Adrenergic, Beta Renal Circulation Synaptosomes Metabolism Tyramine Vascular Resistance |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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