Zipeprol: preclinical assessment of abuse potential.
Zipeprol was evaluated in a number of in vitro and in vivo assays predictive of stimulant, depressant, or opioid abuse potential. Zipeprol had affinity for mu and kappa opioid binding sites as well as sigma binding sites. However, it failed to exert opioid-like agonist actions in rodents, and did not attenuate withdrawal signs in morphine- or pentobarbital-dependent rats. Zipeprol did not substitute for either amphetamine or pentobarbital in drug discrimination assays in rhesus monkeys. On the other hand, it suppressed morphine withdrawal signs in rhesus monkeys in two assays, and it acted as a quadazocine-sensitive reinforcer in monkeys trained to self-inject alfentanil. Zipeprol also acted as a reinforcer in monkeys trained to self-inject methohexital. In a dose range of 10-18 mg/kg, zipeprol induced convulsions in monkeys. Zipeprol appears to have abuse potential and a novel spectrum of action involving both opioid and non-opioid effects.
Department of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0163, USA.
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Acteo
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Bowman
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Butelman
J A
JA
Englis
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Harrish
A E
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Jacobson
M V
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Mattson
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Medzihradsky
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Patrick
J K
JK
Rowlett
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Smith
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Winger
J H
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Woods
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Woolverton
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D004193:Discrimination Learning; D004357:Drug Synergism; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009042:Motivation; D009293:Opioid-Related Disorders / Q000523:psychology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects; D012306:Risk; D015819:Substance Abuse, Intravenous / Q000523:psychology; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D019966:Substance-Related Disorders / Q000523:psychology*
D000996:Antitussive Agents; D010879:Piperazines; D011957:Receptors, Opioid; C013341:zipeprol