Selective affinity of pirenzepine analogues for subtypes of muscarinic receptors

Conference · Wed Mar 05 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:7024786

Stubbins, J F; Smith, J D; Liu, W S; Gulya, K; Yamamura, H I

Pirenzepine (PZ), telenzepine (TZ) and quinuclidinyl xanthene-9-carboxylate (QNX) are antimuscarinic agents containing a tricyclic ring system and a basic side chain that have been reported to have selective affinity for the M/sub 1/ subtype of receptor. They have prepared and examined seven new PZ analogues containing modifications in either the tricyclic ring system, the side-chain, or both. Affinity for M/sub 1/ type receptors was determined by displacement of specifically-bound (/sup 3/H)PZ from rat cerebral cortex homogenates. Affinity for M/sub 2/ type receptors was measured on rat heart homogenate using (/sup 3/H)(-)quinuclidinyl benzilate. The ratio of the K/sub i/'s for M/sub 1/ and M/sub 2/ receptors were calculated and compared to PZ. All of the compounds had a higher affinity for M/sub 1/ than M/sub 2/ receptors. Three of the compounds were comparable to PZ in selectivity, but the more selective compounds had a weaker affinity for M/sub 1/ receptors. TZ and QNX were less selective than PZ.

• Research Organization: Virginia Commonwealth Univ., Richmond
• OSTI ID: 7024786
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:4
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
AFFINITY
AMINES
AMMONIUM COMPOUNDS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
DRUGS
ESTERS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MEMBRANE PROTEINS
NEUROREGULATORS
ORGANIC COMPOUNDS
PARASYMPATHOMIMETICS
PROTEINS
QUATERNARY COMPOUNDS
REACTION KINETICS
RECEPTORS
TRACER TECHNIQUES
TRITIUM COMPOUNDS