Mir, A. K., Hibert, M., Tricklebank, M. D., Middlemiss, D. N., Kidd, Emma Jane ORCID: https://orcid.org/0000-0001-5507-1170 and Fozard, J. R. 1988. MDL 72832: a potent and stereoselective ligand at central and peripheral 5-HT1A receptors. European Journal of Pharmacology 149 (1-2) , pp. 107-120. 10.1016/0014-2999(88)90048-9 |
Abstract
In receptor binding assays (±)MDL 72832, 8-[4-(1,4-benzodioxan-2-ylmethylamino)butyl]8-azaspiro[4,5]decane-7,9-dione, was a potent (pIC50 9.1), selective and stereospecific ligand for central 5-HT1A recognition sites. In functional tests, (±)MDL 72832 and its S(−) and R(+) enantiomers blocked stereoselectively the 8-OH-DPAT-induced neuronal inhibition of the transmurally stimulated guinea-pig ileum and the cardiovascular effects of 8-OH-DPAT in anaesthetized rats. In contrast, (±)MDL 72832 and its enantiomers were exclusively ‘8-OH-DPAT-like’ in their ability to fully and stereoselectively generalize to the 8-OH-DPAT discriminative stimulus and, in reserpinised rats, to induce forepaw treading and flat body posture. These results characterize (±)MDL 73832 as a potent, stereoselective ligand with mixed agonist and antagonist properties at central and peripheral 5-HT1A receptors. The similar stereoselective requirements for the recognition site and functional effects provides compelling evidence that the 5-HT1A recognition site is indeed a functional receptor.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Pharmacy |
Subjects: | R Medicine > RM Therapeutics. Pharmacology |
Uncontrolled Keywords: | MDL 72832; 5-HT1A receptors; Cardiovascular system; Interoceptive cue; Guinea-pig ileum; 8-OH-DPAT; (Stereoselectivity, Agonist, Antagonist, Behaviour, Rat) |
Publisher: | Elsevier |
ISSN: | 0014-2999 |
Last Modified: | 18 Oct 2022 13:38 |
URI: | https://orca.cardiff.ac.uk/id/eprint/14750 |
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