Effects of Three Narcotic Antagonists (Naltrexone, Diprenorphine, and S-20682) on Blood Pressure, Heart Rate and Electrical Cortical Activity

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Abstract
Three narcotic antagonist drugs (EN-1639 or naltrexone, M-5050 or diprenorphine and the 6-oxo analogue of oxilorphan, S-20682) were evaluated in increasing doses (1–80μg/kg) in the unanaesthetised dog for possible effects on blood pressure, heart rate, respiratory rate, arterial blood gases, and convulsive EEG changes. Compared to the control-awake situation, diprenorphine and S-20682 induced hypotension (maximum fall 15%), bradycardia (maximum 12%) and bradypnoea (maximum 25%). These effects were not increased at doses higher than 20 μg/kg. Despite the induced bradypnoea, there were no significant changes in arterial pO2 and pCO2. Simultaneously, with the cardiorespiratory changes, EEG activity shifted from high frequency, low amplitudes of the awake state, to low frequency, high amplitudes of a sleep-like state. Convulsive EEG changes were never recorded with any of the tested compounds. It is suggested that the observed cardiovascular changes are due to a reduced state of vigilance, since auditory stimuli induced an arousal reaction with a reversal of the depressed variables. In contrast, naltrexone induced only bradycardia in the observed dose range (maximum 25 %). There were no effects on blood pressure, respiratory rate, arterial blood gases and EEG.

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