Effects of three narcotic antagonists (naltrexone, diprenorphine, and S-20682) on blood pressure, heart rate and electrical cortical activity.

Authors

Freye, E; Hartung, E; Schenk, G K

Year

1983

Journal

Pharmacology

PMID

6133288

DOI

10.1159/000137792

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 (1-80 micrograms/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 micrograms/kg. Despite the induced bradypnoea, there were no significant changes in arterial pO2 and pCO2. Simultaneously, with the cardio-respiratory 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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