Wellman P J, Tow S, McMahon L
Department of Psychology, Texas A&M University, College Station 77843-4235.
Pharmacol Biochem Behav. 1995 Feb;50(2):287-91. doi: 10.1016/0091-3057(94)00316-b.
Phenylpropanolamine (PPA) suppresses appetite in rats via activation of alpha 1-adrenergic receptors within the paraventricular hypothalamus (PVN). The serotonergic (5-HT) agonist fenfluramine (FEN) is thought to suppress appetite via stimulation of 5-HT release within the PVN rather than activation of adrenergic receptors. Whether a mixture of these neurochemically distinct anorexic drugs will serve as an effective appetite suppressant is unknown. In the present experiment, drug-drug interactions between PPA and FEN were explored using an isobologram technique. Fixed doses of PPA (0 vs. 5 mg/kg) were combined with various doses of FEN (1.25, 2.5, and 5.0 mg/kg) and fixed doses of FEN (0 vs. 2.5 mg/kg) were combined with various doses of PPA (0, 5, 10, and 15 mg/kg). Drug combinations were injected IP 30 min before a 1-h feeding trial in 16-h food-deprived rats. PPA and FEN were dose-additive in this paradigm, an outcome that supports the feasibility of a new appetite suppressant composed of a mixture of PPA and FEN.
苯丙醇胺（PPA）通过激活下丘脑室旁核（PVN）内的α1-肾上腺素能受体来抑制大鼠的食欲。血清素能（5-HT）激动剂芬氟拉明（FEN）被认为是通过刺激PVN内的5-HT释放而非激活肾上腺素能受体来抑制食欲的。这两种神经化学性质不同的厌食药物的混合物是否会成为一种有效的食欲抑制剂尚不清楚。在本实验中，使用等效线图技术探究了PPA和FEN之间的药物相互作用。固定剂量的PPA（0对5mg/kg）与不同剂量的FEN（1.25、2.5和5.0mg/kg）组合，固定剂量的FEN（0对2.5mg/kg）与不同剂量的PPA（0、5、10和15mg/kg）组合。在对16小时未进食的大鼠进行1小时进食试验前30分钟腹腔注射药物组合。在该实验范式中，PPA和FEN具有剂量相加性，这一结果支持了由PPA和FEN混合物组成的新型食欲抑制剂的可行性。
