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Blocking effect of puromycin, ethanol, and chloroform on the development of tolerance to an opiate

1966; Elsevier BV; Volume: 15; Issue: 11 Linguagem: Inglês

10.1016/0006-2952(66)90095-5

1873-2968

Alfred A. Smith, Meta Karmin, Joann Gavitt,

Cancer therapeutics and mechanisms

Alfentanil-midazolam analgesic interactions were studied in rats with continuous infusions or bolus injections of the drugs. Analgesia was determined by measuring the threshold of motor response to noxious pressure. The continous constant-rate infusion of alfentanil demonstrated that after an initial peak, the analgesia profoundly declined due to the development of acute tolerance. When alfentanil (250 μg·kg−1·h−1) was given together with midazolam (3 mg·kg−1·h−1), the decline in the analgesic effect of alfentanil was attenuated. Following the 4 h period of the constant-rate (250 μg·kg−1·h−1) infusion of alfentanil, when acute tolerance was already developed, midazolam (3 mg·kg−1) given as a bolus injection enhanced the alfentanil-induced anesthesia. At the same time, when alfentanil was given as a bolus injection (30 μg·kg−1) with or without midazolam (3 mg·kg−1) also by bolus injection, no changes were seen to indicate an enhancement of the analgesic effect of alfentanil by midazolam. The results suggest that midazolam attenuates the development of acute tolerance to the analgesic effect of alfentanil.