Effect of CP-96,345, a Nonpeptide Substance P Receptor Antagonist, on Salivation in Rats

CP-96,345 {(2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1 -azabicyclo[2.2.2]octa N-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...

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Veröffentlicht in:	Proceedings of the National Academy of Sciences - PNAS 1991-11, Vol.88 (22), p.10042-10044
Hauptverfasser:	Snider, R. Michael, Longo, Kelly P., Drozda, Susan E., Lowe, John A., Leeman, Susan E.
Format:	Artikel
Sprache:	eng
Schlagworte:	550201 - Biochemistry- Tracer Techniques ACETYLCHOLINE Agonists AMINES AMMONIUM COMPOUNDS ANESTHETICS ANIMALS Antagonists ANTICONVULSANTS AUTONOMIC NERVOUS SYSTEM AGENTS AZINES BARBITURATES BASIC BIOLOGICAL SCIENCES Binding, Competitive BIOCHEMICAL REACTION KINETICS Biological and medical sciences BIOLOGICAL MATERIALS Biphenyl Compounds - pharmacology BODY BODY FLUIDS CARBOHYDRATES Cell Membrane - metabolism CENTRAL NERVOUS SYSTEM DEPRESSANTS Dosage Dose-Response Relationship, Drug DOSE-RESPONSE RELATIONSHIPS DRUGS Enantiomers Ent. Stomatology ESTERS GLANDS HETEROCYCLIC COMPOUNDS HYDROGEN COMPOUNDS HYPNOTICS AND SEDATIVES INHIBITION INJECTION INTAKE INTRAPERITONEAL INJECTION ISOTOPE APPLICATIONS KINETICS KININS Male MAMMALS MATERIALS Medical sciences MEMBRANE PROTEINS MONOSACCHARIDES NEUROREGULATORS ORAL ADMINISTRATION ORGANIC COMPOUNDS ORGANIC NITROGEN COMPOUNDS ORGANIC OXYGEN COMPOUNDS ORGANS PARASYMPATHOMIMETICS Parotid Gland - drug effects Parotid Gland - physiology PEPTIDES Pharmacology Pharmacology. Drug treatments PHENOBARBITAL POLYPEPTIDES PROTEINS PYRIMIDINES QUATERNARY COMPOUNDS RADIORECEPTOR ASSAY RATS Rats, Inbred Strains REACTION KINETICS RECEPTORS Receptors, Neurokinin-1 Receptors, Neurotransmitter - antagonists & inhibitors Receptors, Neurotransmitter - drug effects Receptors, Neurotransmitter - physiology RODENTS SACCHARIDES SALIVA Saliva - drug effects Saliva - metabolism SALIVARY GLANDS Salivation SIALIC ACID Sodium Submandibular Gland - drug effects Submandibular Gland - physiology Substance P - metabolism Substance P - pharmacology TRACER TECHNIQUES TRITIUM COMPOUNDS VERTEBRATES
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Zusammenfassung:	CP-96,345 {(2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1 -azabicyclo[2.2.2]octa N-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, with a median effective dose of 12-24 μmol/kg (5-10 mg/kg) of body weight, but had no effect on acetylcholine-stimulated salivation. CP-96,345 produced concentration-dependent inhibition of [3H]substance P binding to rat submaxillary gland membranes, with a median effective concentration of 34 ± 3.6 nM. These biological activities were confined to CP-96,345 in that the 2R,3R enantiomer (CP-96,344) was without effect.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.88.22.10042