title: The putative 5-HT1B receptor agonist CP-93,129 suppresses rat hippocampal 5-HT release in vivo: comparison with RU 24969.
abstract: We have compared the ability of the new putatively specific 5-HT1B receptor agonist CP-93,129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b] pyrid-5-one) and the structurally related mixed 5-HT1A/5-HT1B receptor ligand RU 24969, to influence 5-HT release in brain in vivo, using microdialysis techniques in chloral hydrate-anaesthetised rats. CP-93,129 (3 or 10 microM, via the dialysis perfusion medium) caused a concentration-dependent and methiothepin (10 microM)-sensitive suppression of ventral hippocampal 5-HT output. The effect of RU 24969 on 5-HT output was dependent on whether or not the 5-HT reuptake blocker citalopram was present in the perfusion medium. Thus, RU 24969 (0.1 microM) induced a decrease, or an increase followed by a decrease (1 microM), in 5-HT output in the absence of citalopram, but monotonically decreased (1 microM) 5-HT release when citalopram (1 microM) was present. CP-93,129 decreased dialysate 5-HT in either condition. Our findings are consistent with the characterisation of CP-93,129 as a 5-HT1B receptor agonist, and may thus represent in vivo support for 5-HT1B autoreceptor-mediated feedback control of 5-HT release in the rat brain. The 5-HT1B selectivity of CP-93,129, and its lack of 5-HT reuptake blocking properties, suggests that the compound compares favourably with other purported 5-HT1B receptor agonists.
authors.affiliation: Department of Pharmacology, University of Göteborg, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Hjorth
authors.forename: R
authors.initials: R
authors.lastname: Tao
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology; D003956:Dialysis; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*
chemical_list: D007211:Indoles; D011725:Pyridines; D011758:Pyrroles; D011985:Receptors, Serotonin; D015283:Citalopram; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D008719:Methiothepin