Effect of tricyclic antidepressants on transmitter-stimulated inositol phosphate production in rat brain cortex in vitro

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5326476

Nomura, S; Enna, S J

Tricyclic antidepressants (TCAs) have anticholinergic and ..cap alpha..-adrenergic blocking properties. The present study was undertaken to examine the effects of amitriptyline, imipramine, and desipramine on inositol phosphate accumulation, a brain second messenger system associated with cholinergic and adrenergic receptors. Whereas the TCAs were 28 to 400-fold weaker than atropine as inhibitors of /sup 3/H-QNB binding to brain cholinergic receptors, they were 600 to 2000-fold less active than atropine as inhibitors of carbachol-stimulated IP accumulation in brain. In contrast, the relative potencies of the TCAs and prazosin to inhibit norepinephrine-stimulated IP accumulation and /sup 3/H-prazosin binding appeared to be similar in the two assays. The results suggest pharmacological differences between the cholinergic receptors labeled in the ONB binding assay and those mediating the IP response, whereas the ..cap alpha../sub 1/-adrenergic receptors appear to be similar in the two systems. Since atropine is considered a nonselective muscarinic antagonist, it is possible that the TCAs may differentiate between cholinergic receptor subtypes, which may be an important component of their clinical response.

• Research Organization: Univ. of Texas Medical School, Houston
• OSTI ID: 5326476
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
ALKALOIDS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
ANTIDEPRESSANTS
ATROPINE
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOSYNTHESIS
BODY
BRAIN
CARBOHYDRATES
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CHOLINE
DRUGS
HYDROXY COMPOUNDS
IN VITRO
INOSITOL
INOSITOLS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIPOTROPIC FACTORS
MAMMALS
MEMBRANE PROTEINS
MONOSACCHARIDES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PARASYMPATHOLYTICS
PHOSPHATES
PHOSPHORUS COMPOUNDS
PROTEINS
PSYCHOTROPIC DRUGS
QUATERNARY COMPOUNDS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SACCHARIDES
SYMPATHOMIMETICS
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES