Influence of pretreatment with a monoamine oxidase inhibitor (phenelzine) on the effects of buprenorphine and pethidine in the conscious rabbit.
The existence of a severe toxic interaction (occasionally fatal) from the clinical use of pethidine and monoamine oxidase (MAO) inhibitors is well established. The present study evaluates the possibility of such an interaction existing for the opioid partial agonist buprenorphine. Conscious rabbits (n = 6 in each group) pretreated 18-24 h previously with physiological saline or the MAO inhibitor phenelzine 20 mg kg-1 s.c. were subsequently given physiological saline, pethidine 5 mg kg-1 i.v. or buprenorphine 0.1 or 1.0 mg kg-1 i.v. Whilst saline was without effect and phenelzine produced only a small increase in the rabbit temperature, the combination of phenelzine and pethidine produced a marked, prolonged hyperpyrexia (+4.4 +/- 0.19 degrees C; P less than 0.001), hypertension (+33.9 +/- 3.1 mm Hg; P less than 0.01) and agitation. Three rabbits died, at 35, 45 and 55 min after the pethidine-phenelzine combination. Buprenorphine was without significant effect on any parameter when given after phenelzine. In the model used buprenorphine, in contrast to pethidine, showed no interaction with the MAO inhibitor phenelzine.
Mackenzie
J E
JE
Department of Biology, Reckitt and Colman Pharmaceutical Division, Hull, North Humberside.
Frank
L W
LW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002047:Buprenorphine / Q000009:adverse effects*; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008614:Meperidine / Q000009:adverse effects*; D010624:Phenelzine / Q000008:administration & dosage / Q000009:adverse effects*; D011817:Rabbits; D013997:Time Factors
D002047:Buprenorphine; D008614:Meperidine; D010624:Phenelzine