title: Studies of the pharmacology and pathology of intrathecally administered 4-anilinopiperidine analogues and morphine in the rat and cat.
abstract: In rats, intrathecal alfentanil, lofentanil, sufentanil, fentanyl, and morphine produced dose-dependent elevations in the hot-plate and tail-flick latencies and a powerful suppression of the writhing response. The slopes of the monotonic dose-response curves for the five opioids did not differ significantly. In terms of the hot-plate ED50 after intrathecal injection, the order of potency was as follows: lofentanil (210), sufentanil (29), fentanyl (3), morphine (1), and alfentanil (1). Comparable results were observed in the tail flick. The duration of action was proportional to dose. However, at doses that produced an equal magnitude of inhibition, the duration of action was lofentanil greater than morphine greater than sufentanil greater than alfentanil greater than or equal to fentanyl. Systemically administered naloxone (0.03-1 mg/kg, sc) resulted in dose-dependent antagonism of the antinociceptive effect of intrathecal morphine, fentanyl, alfentanil, and sufentanil. In contrast, intrathecal lofentanil was extremely resistant to antagonism by naloxone. In cats, similar dose-dependent blockade of the thermally evoked skin-twitch response was observed after intrathecal morphine, sufentanil, alfentanil, and fentanyl. As in the rat, the slope of the monotonic dose-response curves did not differ. The relative potency and duration of action after equipotent intrathecal doses were similar to those observed in the rodent. These results suggest that sufentanil, alfentanil, and fentanyl exert their analgesic effects in vivo at a spinal cord site that has properties comparable to those of the site acted upon by morphine. Except for catalepsy in rats, no major behavioral dysfunctions were noted at the ED50 dose of any of the drugs administered. No abnormal morphologic effects of acutely or chronically administered alfentanil and sufentanil were seen, aside from an inflammatory reaction secondary to catheter placement.
authors.forename: T L
authors.initials: TL
authors.lastname: Yaksh
authors.forename: R Y
authors.initials: RY
authors.lastname: Noueihed
authors.forename: P A
authors.initials: PA
authors.lastname: Durant
mesh_terms: D015760:Alfentanil; D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002404:Catheterization / Q000009:adverse effects; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D007278:Injections, Spinal; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D017409:Sufentanil; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D015760:Alfentanil; D009270:Naloxone; D009020:Morphine; C034846:lofentanil; D017409:Sufentanil; D005283:Fentanyl