Reversal by naloxone of the effects of morphine on the unanesthetized dog
Jacob, J.J.; Michaud, G.M.
Archives Internationales de Pharmacodynamie et de Therapie 222(2): 322-340
1976
ISSN/ISBN: 0003-9780 PMID: 984983 Document Number: 96672
In unasthetized dogs naloxone induced effects opposed to those of morphine (tachycardia, agitation, hyperthermia, tachypnea) and mydriasis. These effects were moderate and transient; some of them were elicited with low doses being border-line after 0.03 mg.kg-1 s.c., statistically significant after 0.1 mg.kg-1 s.c.; they increased slightly with the dose. After repeated administrations, acute tolerance developed and some moderate morphine-like effects (miosis, sedation) were observed. The stimulatory effects described here may result from antagonism of a morphinomimetic natural ligand,and represent thus indirect arguments in favour of normal functions of this ligand; these functions would be to temper not only algesic but also other stimulant reactions. The limitation of the effects might result from the limited release of this ligand in normal dogs and (or) from interfering morphinomimetic properties of naloxone, which are apparently unmasked when administrations are repeated. Both, stimulatory and inhibitory effects of naloxone are not liable to represent noticeable side-effects of this drug, but they both might play some role in the mechanisms of precipitated abstinence.