Assessment of the abuse potential of acetorphan, an enkephalinase inhibitor.
The discriminative stimulus properties, reinforcing effects and physical dependence potential of acetorphan, a parenterally-active enkephalinase (E.C. 3.4.21.11) inhibitor, were assessed in the present studies. Rats trained to discriminate 2 mg/kg morphine from saline did not generalize to acetorphan at any dose tested (5-50 mg/kg). Acetorphan also had minimal reinforcing effects in rhesus monkeys. When acetorphan was substituted for cocaine, one dose (300 micrograms/kg per inj.) maintained responding somewhat above the range of vehicle values in only two of the four monkeys tested. In physical dependence studies, acetorphan also failed to produce opioid-like effects. In morphine-dependent monkeys and rats, acetorphan failed to suppress withdrawal. Additionally, there were no overt withdrawal signs observed following the termination of chronic acetorphan infusion in the rat. Together, these results indicate that acetorphan appears to have minimal abuse potential.
Knisely
J S
JS
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.
Beardsley
P M
PM
Aceto
M D
MD
Balster
R L
RL
Harris
L S
LS
D000818:Animals; D003042:Cocaine; D004192:Discrimination, Psychological; D005260:Female; D008253:Macaca mulatta; D008297:Male; D009021:Morphine Dependence / Q000503:physiopathology; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D019966:Substance-Related Disorders / Q000209:etiology*; D015244:Thiorphan / Q000031:analogs & derivatives*
C049331:racecadotril; D015244:Thiorphan; D015260:Neprilysin; D003042:Cocaine