Down-regulation of tryptamine receptors following chronic administration of clorgyline.
Chronic treatment with clorgyline, a type A monoamine oxidase (MAO) inhibitor (1 mg/kg/day for 11 days), reduced the number (Bmax) but not the affinity (Kd) of [3H]tryptamine binding sites in rat frontal/parietal cortical membranes. Binding was reduced for at least 36 days following the last injection. The reduction in [3H]tryptamine binding was dose-related and appeared to be maximal following a daily dose of 3 mg/kg. Chronic treatment with deprenyl, a type B MAO inhibitor (1 mg/kg/day for 11 days), did not affect [3H]tryptamine binding. Acute clorgyline administration (11 mg/kg) also had no effect. These data suggest that [3H]tryptamine binds to neurotransmitter receptors for tryptamine since mere chemical recognition sites would not be expected to be modulated by chronic drug treatment. Also, since [3H]tryptamine binding was down-regulated by a type A, but not a type B, MAO inhibitor, tryptamine may be selectively metabolized by type A MAO in vivo.
Martin
L L
LL
Pharmaceuticals Division, CIBA-GEIGY Corporation, Summit, NJ 07901.
Neale
R F
RF
Wood
P L
PL
D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003010:Clorgyline / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D011437:Propylamines / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D014363:Tryptamines / Q000493:pharmacokinetics
D011437:Propylamines; D011985:Receptors, Serotonin; D014363:Tryptamines; C030820:tryptamine; D003010:Clorgyline