Buspirone and gepirone: partial agonists at the 5HT/sub 1/A receptor linked to adenylate cyclase (AC) in rat and guinea pig hippocampal preparations

Conference · Sat Mar 01 00:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5508025

Yocca, F D; Hyslop, D K; Taylor, D P; Maayani, S

The pharmacologic nature of the 5-HT receptor that is negatively linked to AC in membrane preparations from rat and guinea pig (gp) brain in cell culture and in gp hippocampal homogenates positively linked to AC seem to be indistinguishable from the 5HT/sub 1A/ binding site in similar preparations. Affinity values of chemically unrelated but selective drugs for a binding site are useful for taxonomy of functional receptors. The novel anxiolytic drug buspirone (B) and its analog gepirone (G) exhibit selectivity and affinity for spiperone-sensitive (/sup 3/H)-5-HT and (/sup 3/H)-8-OH-DPAT binding sites in gp and rat hippocampus. In the two species tested, B and G were partial agonists (intrinsic activity approx. = 0.5) compared to 5-HT and its potent analog 5-carboxamideotryptamine (5-COAT) at the 5-HT/sub 1A/ receptor linked to AC. The K/sub B/ value of spiperone determined with B and G was indistinguishable from that determined with 5-HT and 5-COAT (20-30 nM). Since B and G exert unique agonist effects at the functional 5HT/sub 1A/ receptor, their structures may be important for identifying chemical groups necessary for recognition and activation of the 5HT/sub 1A/ receptor.

• Research Organization: Bristol-Meyers Co., Evansville, IN
• OSTI ID: 5508025
• Report Number(s): CONF-8604222-; TRN: 86-026630
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
SEROTONIN
RECEPTORS
SYMPATHOMIMETICS
BIOCHEMICAL REACTION KINETICS
AFFINITY
CELL MEMBRANES
CYCLASES
GUINEA PIGS
HIPPOCAMPUS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BODY
BRAIN
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
DRUGS
ENZYMES
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LYASES
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RODENTS
TRYPTAMINES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques