Use of the chronic spinal dog for the assessment of the abuse potentiality and utility of narcotic analgesics and narcotic antagonists

Abstract

In the chronic spinal dog, prototypic drugs from all chemical classes thus far studied suppressed abstinence in a dose-related manner and valid bioassays were obtained. There is a good correlation between relative potencies in dog and man. Similarly, the partial agonists buprenorphine and profadol partially suppressed abstinence in the chronic spinal dog, and the slopes of their suppression dose response lines were less steep than that of morphine. Propiram was more effective in suppressing abstinence than either buprenorphine or profadol and thus in the dog appears to be an agonist with a higher activity than either buprenorphine or profadol. Further, both buprenorphine and propiram precipitated abstinence in the stabilized morphine-dependent dog. Profadol precipitation studies have not yet been conducted in the dog. Both profadol and propiram precipitate abstinence in man. Thus, the morphine-dependent chronic spinal dog is useful in identifying partial agonists of the morphine type and yields results comparable with those obtained in man. Meperidine, codeine, and normorphine are not typical agonists of the morphine type in either the dog or man. There is a good correlation between the potency of antagonists in dog and man, as well as between their associated agonistic activity.