Effects of imipramine on tyrosine and tryptophan are mediated by beta-adrenoceptor stimulation.
Imipramine (IMI; 20 mg/kg) in rats decreased the plasma tyrosine concentration by 21% (90 min), whereas norepinephrine (NE; 1.25 mg/kg) raised it by 72% (40 min). Since NE raised plasma tyrosine by stimulating alpha-adrenoceptors, as shown by phenoxybenzamine (PB) completely abolishing this increase, an experiment was done to find out whether IMI lowered plasma tyrosine by blocking alpha-adrenoceptors. In contrast to PB, IMI pretreatment failed to alter the NE-induced elevation in plasma tyrosine, suggesting that at this dose IMI is not an effective alpha-adrenergic antagonist in vivo. Thus, IMI would not appear to reduce plasma tyrosine by blocking alpha-adrenoceptors. In a separate experiment, propranolol blocked the ability of IMI to lower plasma tyrosine. Propranolol also prevented a 17% elevation in brain tryptophan levels induced by IMI but did not alter the 29% decrease in plasma tryptophan. PB by itself decreased plasma tyrosine, but this decrease was not greater by additionally treating with IMI. Salbutamol (10 mg/kg), a beta 2 agonist, lowered plasma tyrosine to 76% and raised brain tryptophan to 143% of control. These results suggest that IMI decreases tyrosine concentrations in plasma and raises tryptophan in brain by stimulating beta-adrenoceptors.
Edwards
D J
DJ
Department of Pharmacology-Physiology, University of Pittsburgh School of Dental Medicine, PA 15261.
Sorisio
D A
DA
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000032:analysis; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014364:Tryptophan / Q000032:analysis / Q000097:blood*; D014443:Tyrosine / Q000032:analysis / Q000097:blood*
D011943:Receptors, Adrenergic, beta; D014443:Tyrosine; D008734:Methoxyhydroxyphenylglycol; D014364:Tryptophan; D007099:Imipramine; D009638:Norepinephrine