Antagonism of xylazine-induced depression of shuttle-avoidance responses in dogs by administration of 4-aminopyridine, doxapram, or yohimbine.

The effectiveness of 4-aminopyridine, doxapram, or yohimbine as antagonists against xylazine-induced CNS depression in dogs was evaluated and compared, using the 2-way shuttle-avoidance paradigm. All drugs were given IV to 5 male dogs trained to avoid mild shock by jumping over a hurdle within 10 s after initiation of an audible tone. At dosages of 1 and 2 mg/kg of body weight, xylazine abolished or significantly decreased the mean number of avoidance responses and significantly increased the mean latency of avoidance responses. The analeptic 4-aminopyridine (0.5 mg/kg) did not significantly antagonize xylazine in all dogs. One dog convulsed both times it was given xylazine followed by 4-aminopyridine, but did not convulse when given either drug alone. Doxapram (5.5 mg/kg), a short-acting analeptic and respiratory stimulant, was only partially effective in antagonizing xylazine, and its antagonistic actions were brief. Yohimbine (0.1 mg/kg), an alpha 2-adrenoreceptor-blocking agent, was superior to 4-aminopyridine and doxapram in its ability to antagonize xylazine-induced CNS depression. Yohimbine consistently increased the mean number of avoidance responses to the maximum of 8 and consistently decreased the mean latency of avoidance responses to control values in dogs given 1 or 2 mg of xylazine/kg. In dogs given 2 mg of xylazine/kg, yohimbine was significantly more effective than 4-aminopyridine or doxapram in its ability to increase the mean number of avoidance responses and decrease the mean latency of avoidance responses.(ABSTRACT TRUNCATED AT 250 WORDS)