Effect of CP-96,345, a nonpeptide substance P receptor antagonist, on salivation in rats

Journal Article · Fri Nov 15 04:00:00 EST 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.22.10042· OSTI ID:5822158

Snider, R M; Longo, K P; Drozda, S E; Lowe, III, J A ^[1]; Leeman, S E ^[2]

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1. Pfizer, Inc., Groton, CT (United States)
2. Univ. of Massachusetts Medical School, Worcester, MA (United States)

CP-96,345 ((2S, 3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)methyl)-1-azabicyclo(2.2.2)octan-3-amine) antagonism of substance P-stimulated salivation was investigated in pentobarbital-anesthetized rats. Administered either intraperitoneally or orally, CP-96,345 produced dose-dependent inhibition of the sialogogic response elicited by substance P but had no effect on acetylcholine-stimulated salivation. CP-96,345 produced concentration-dependent inhibition of ({sup 3}H)substance P binding to rat submaxillary gland membranes, with a median effective concentration of 34{plus minus}3.6 nM. These biological activities were confined to CP-96,345 in that the 2R, 3R enantiomer (CP-96,344) was without effect.

• OSTI ID: 5822158
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:22; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
AMINES
AMMONIUM COMPOUNDS
ANESTHETICS
ANIMALS
ANTICONVULSANTS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
BARBITURATES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BODY
BODY FLUIDS
CARBOHYDRATES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ESTERS
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYPNOTICS AND SEDATIVES
INHIBITION
INJECTION
INTAKE
INTRAPERITONEAL INJECTION
ISOTOPE APPLICATIONS
KINETICS
KININS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MONOSACCHARIDES
NEUROREGULATORS
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
PEPTIDES
PHENOBARBITAL
POLYPEPTIDES
PROTEINS
PYRIMIDINES
QUATERNARY COMPOUNDS
RADIORECEPTOR ASSAY
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SACCHARIDES
SALIVA
SALIVARY GLANDS
SIALIC ACID
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES