Jacob J J, Michaud G M
Arch Int Pharmacodyn Ther. 1976 Aug;222(2):322-40.
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.
在未麻醉的犬中，纳洛酮产生的效应与吗啡相反（心动过速、躁动、体温过高、呼吸急促）以及瞳孔散大。这些效应程度适中且短暂；其中一些效应在皮下注射0.03mg·kg-1时处于临界状态，皮下注射0.1mg·kg-1时具有统计学意义，且随着剂量增加而略有增强。重复给药后，会产生急性耐受性，并观察到一些中等程度的类吗啡效应（瞳孔缩小、镇静）。此处描述的刺激效应可能源于对拟吗啡天然配体的拮抗作用，因此代表了支持该配体正常功能的间接证据；这些功能不仅会缓和痛觉，还会缓和其他刺激反应。效应的局限性可能源于正常犬体内该配体的有限释放和（或）纳洛酮的拟吗啡特性的干扰，当重复给药时，这些特性显然会显现出来。纳洛酮的刺激和抑制效应均不太可能代表该药物明显的副作用，但它们都可能在戒断反应的机制中发挥一定作用。
