EFFECTS OF SOME PHENYLETHYLAMINES IN RHESUS-MONKEYS TRAINED TO DISCRIMINATE (-AMPHETAMINE FROM SALINE())

Although the structure-activity relationships (SAR) for the discrimina tive stimulus (DS) effects of phenylethylamines (PEAs) have been exten sively evaluated in rats, only isolated components of the SAR have bee n studied in other species. Since DS effects in animals predict subjec tive effects in humans, it is important to establish cross-species gen erality of substitution results. In the present experiment, rhesus mon keys (n = 4) were trained to discriminate (+)-amphetamine (0.56 or 1.0 mg/kg, i.g.) from saline in a two-lever drug discrimination paradigm. Responding was maintained under a fixed-ratio discrete-trials schedul e of shock avoidance. (+)-Amphetamine, (-)-amphetamine, and the N-subs tituted phenylethylamines (+)-methylamphetamine, and (+)-ethylamphetam ine all engendered dose-dependent, full substitution for (+)-amphetami ne and had no effect on rate of responding. In contrast, the ring-subs tituted compounds (+/-)-4-methoxyamphetamine (PMA), (+/-)-2,5-dimethox y-4-methylamphetamine (DMA), (+/-)-2,5-dimethoxy-4-methylamphetamine ( DOM), and (+/-)-3,4,5-trimethoxyamphetamine (TMA) occasioned little or no (+)-amphetamine-appropriate response up to doses of 3.0 or 10 mg/k g. Therefore, it appears that monkeys respond to N-substituted ampheta mines in the same way as rats, at least qualitatively. Considering tha t ring-substituted compounds have been found to partially substitute f or (+)-amphetamine in rats, it is possible that the (+)-amphetamine DS may be pharmacologically more selective in monkeys. However, methodol ogical differences may also explain differences between experiments. ( C) 1997 Elsevier Science Ireland Ltd.