Antagonism of xylazine sedation with yohimbine, 4-aminopyridine, and doxapram in dogs.
Groups of atropinized dogs (6 dogs/group) were sedated with xylazine (2.2 mg/kg of body weight, IM). At recumbency, the dogs were given IV saline solution (control groups), yohimbine (0.05, 0.1, and 0.2 mg/kg), 4-aminopyridine (4-AP; 0.3, 0.6, and 0.9 mg/kg), doxapram (0.5, 1.0, 2.0, and 4.0 mg/kg), or the smallest dose of these antagonists in dual combinations or in triple combination. Two additional groups were sedated with an overdose of xylazine (11 mg/kg, IM). At recumbency, 1 of these groups was given saline solution IV and the other group was given yohimbine IV (0.4 mg/kg) as the antagonist. With the 2.2 mg/kg dose of xylazine, control mean arousal time (MAT) and mean walk time (MWT) were 15.5 minutes and 24.8 minutes, respectively. These values were decreased by the individual antagonists to 0.5 to 2.5 minutes and 0.9 to 7.4 minutes, respectively. Approximate equipotent doses of antagonists (mg/kg) were: yohimbine, 0.2; 4-AP, 0.6; and doxapram, 0.5. Relapses did not occur after yohimbine or 4-AP. With doxapram, muscle tremors and spasms, abnormal postures, or aggressive behavior occurred in several dogs and several dogs had partial or complete relapses. The small doses of individual antagonists were synergistic with regard to MAT, MWT, and duration of residual sedation, but the various combinations of antagonists were not more effective in these regards than were larger doses of the single antagonists. With the overdose of xylazine, control MAT and MWT were 41.5 minutes and 144.5 minutes, respectively. Yohimbine decreased these values to 2.2 minutes and 2.5 minutes, respectively. Relapses did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)
Hatch
R C
RC
Kitzman
J V
JV
Zahner
J M
JM
Clark
J D
JD
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004285:Dogs / Q000502:physiology*; D004315:Doxapram / Q000494:pharmacology*; D004338:Drug Combinations; D005260:Female; D007103:Immobilization; D008124:Locomotion / Q000187:drug effects; D008297:Male; D013843:Thiazines / Q000037:antagonists & inhibitors*; D014991:Xylazine / Q000037:antagonists & inhibitors*; D015016:Yohimbine / Q000494:pharmacology*
D000631:Aminopyridines; D000697:Central Nervous System Stimulants; D004338:Drug Combinations; D013843:Thiazines; D014991:Xylazine; D015016:Yohimbine; D004315:Doxapram; D015761:4-Aminopyridine