Hull K M, Maher T J
Department of Pharmacology, Massachusetts College of Pharmacy, Boston 02115.
Pharmacol Biochem Behav. 1991 Jul;39(3):755-9. doi: 10.1016/0091-3057(91)90159-y.
We have recently reported the ability of L-tyrosine (L-TYR) to potentiate the anorectic activity of various mixed-acting sympathomimetics including phenylpropanolamine (PPA), l-ephedrine (EPH) and d-amphetamine (AMP). Included in those studies was the attenuation of L-TYR's effect when coadministered with L-valine, a large neutral amino acid which competes with L-TYR for uptake into the brain, suggesting a central locus for the action of L-TYR. To determine to what extent L-TYR can potentiate peripheral actions, we investigated the effects of L-TYR with either PPA (20 mg/kg), EPH (20 mg/kg) or AMP (1.75 mg/kg) on gastric transit, gastric retention and intrascapular brown adipose tissue thermogenesis. In each of the paradigms studied, PPA, EPH and AMP significantly increased the expected sympathomimetic-mediated response, but no potentiation of L-TYR was observed. These results are consistent with the hypothesis that L-TYR potentiates the anorectic activity of the mixed-acting sympathomimetics largely via an action at a central locus.
我们最近报道了L-酪氨酸(L-TYR)增强各种混合作用拟交感神经药(包括苯丙醇胺(PPA)、L-麻黄碱(EPH)和d-苯丙胺(AMP))的厌食活性的能力。这些研究包括当与L-缬氨酸共同给药时L-TYR作用的减弱,L-缬氨酸是一种与L-TYR竞争进入大脑的大中性氨基酸,这表明L-TYR的作用位点在中枢。为了确定L-TYR能在多大程度上增强外周作用,我们研究了L-TYR与PPA(20mg/kg)、EPH(20mg/kg)或AMP(1.75mg/kg)对胃排空、胃潴留和肩胛间棕色脂肪组织产热的影响。在所研究的每种范式中,PPA、EPH和AMP均显著增加了预期的拟交感神经介导的反应,但未观察到L-TYR的增强作用。这些结果与以下假设一致,即L-TYR主要通过在中枢位点的作用来增强混合作用拟交感神经药的厌食活性。