Reinforcing and discriminative-stimulus effects of ephedrine isomers in rhesus monkeys

Ephedrine is a sympathomimetic drug that is currently found in many over-th e-counter preparations. This compound exists as four isomers which. in addi tion to a racemic mixture, were evaluated for their positive reinforcing ef fects and for their similarity to (+)-amphetamine as a discriminative stimu lus. Rhesus monkeys (N=3) with intravenous cocaine (0.1 mg/kg/inj) or salin e as a consequence for lever pressing were shown to self-administer all of the ephedrine compounds (range tested: 0.03-3.0 mg/kg/inj), with the except ion of (-)-pseudoephedrine, when each drug/dose was substituted for cocaine or saline during test sessions. However, the (-)-pseudoephedrine isomer wa s evaluated within a limited dose range due to solubility limitations. Syst ematically increasing the number of responses required for an injection ind icated that these isomers were not as effective as reinforcers as was cocai ne. Rhesus monkeys (N=3) trained to discriminate intragastric 1.0 mg/kg (+) -amphetamine from saline were given substitution tests with the ephedrine i somers and the racemic mixture. When given intragastrically, at least one d ose of all the ephedrine isomers substituted for the (+)-amphetamine discri minative stimulus in at least one of the subjects tested. However, (+)-amph etamine-like effects were not systematically related to dose, When the disc riminative-stimulus effects of (-)-ephedrine were also compared with those of (+)-amphetamine across three different routes of administration, full, d ose-related, (+)-amphetamine-like responding was observed with both the int ramuscular and intravenous routes. Taken together, these results suggest th at the ephedrines have psychomotor stimulant-like abuse potential, lower th an that of cocaine. Parenteral administration may enhance psychomotor-stimu lant-like effects. (C) 2001 Elsevier Science Ireland Ltd. All rights reserv ed.