Dexfenfluramine lacks amphetamine-like abuse potential.
1. The amphetamine-like abuse potential of dexfenfluramine (dFEN) was evaluated using drug discrimination and self-administration procedures. 2. Male Fischer rats were trained to discriminate either dFEN (1.0 mg/kg) or d-amphetamine (dAMP; 1.0 mg/kg) from saline in a two-choice discrete-trial avoidance paradigm. 3. In dAMP-trained rats, dFEN (0.5-4.0 mg/kg) engendered almost exclusively saline-appropriate responding. In dFEN-trained rats, dAMP (1.0-4.0 mg/kg) engendered entirely saline-appropriate responding in 3 of 6 rats and intermediate levels of dFEN-appropriate responding in the remaining animals. 4. Potential reinforcing effects of dFEN were also evaluated in 3 male rhesus monkeys trained to self-administer cocaine (i.v.) during daily 60 min sessions under a fixed-ratio (FR)-10 schedule. 5. Various doses of dFEN (30-1000 micrograms/kg/infusion) and dAMP (10 micrograms/kg/infusion) were substituted for cocaine in 4 consecutive daily sessions. In all subjects, dFEN maintained rates of self-administration within the range of rates maintained by saline and considerably below those maintained by cocaine and dAMP. Furthermore, the within-session distribution of responding with dFEN resembled that produced by saline. 6. Taken together, these results strongly suggest that dFEN will not have amphetamine-like abuse potential in humans.
Locke
K W
KW
Interneuron Pharmaceuticals Inc., Lexington, MA, USA.
Levesque
T R
TR
Nicholson
K L
KL
Balster
R L
RL
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005277:Fenfluramine / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012646:Self Administration; D019966:Substance-Related Disorders
D005277:Fenfluramine; D000661:Amphetamine