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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ho, M. Hunter, A. J. Brown, F. Murkitt, K. L. Middlemiss, D. N. Watson, J. M. Wood, M. D. |
| Description | Author Affiliation: Wood MD ( Neuroscience Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex.) |
| Abstract | 1. This study describes the pharmacological comparison of the muscarinic partial agonists sabcomeline, xanomeline and milameline at human cloned muscarinic receptor subtypes (hM1-5). 2. Radioligand binding studies at the hM1-5 muscarinic receptor subtypes were compared with functional studies using microphysiometry using carbachol as the standard full agonist. 3. In binding assays none of the compounds studied displayed preferential affinity for the M1,3,4 or M5 subtypes although carbachol was less potent at hM1 than hM3,4,5. 4. In functional studies, all of the compounds studied displayed similar levels of efficacy across the muscarinic receptors with the exception of M3, where there was a large apparent receptor reserve and the compounds behaved essentially as full agonists. 5. Sabcomeline was the most potent agonist in functional studies but also showed the lowest efficacy. In terms of potency, xanomeline showed some selectivity for M1 over M2 receptors and milameline showed some selectivity for M2 over M1 receptors. 6. These results show the value of microphysiometry in being able to compare receptor pharmacology across subtypes irrespective of the signal transduction pathway. 7. None of the partial agonists showed functional selectivity for M1 receptors, or indeed any muscarinic receptor, in the present study. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 7 |
| Volume Number | 126 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-04-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Muscarinic Agonists Pharmacology Receptors, Muscarinic Drug Effects Animals CHO Cells Cricetinae Quinuclidinyl Benzilate Metabolism Radioligand Assay Receptor, Muscarinic M1 Receptor, Muscarinic M2 Receptor, Muscarinic M3 Receptor, Muscarinic M4 Physiology Comparative Study |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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