Antagonism of xylazine sedation by 4-aminopyridine and yohimbine in cattle.
Twenty-four crossbred steers (4 groups of 6 steers each) were injected IM with a standard dosage range of xylazine hydrochloride (0.2 to 0.3 mg/kg of body weight). When the steers were maximally sedated, group I (control group) were given isotonic saline solution (1 ml, IV), group II were given 4-aminopyridine (4-AP, 0.3 mg/kg) IV, group III were given yohimbine hydrochloride (0.125 mg/kg) IV, and group IV were given 4-AP (0.3 mg/kg) plus yohimbine hydrochloride (0.125 mg/kg) IV. The 4-AP decreased mean standing time (MST; time until animal could stand unaided) from 94.3 minutes (control) to 13.4 minutes. Yohimbine decreased MST to 27 minutes. The combination of 4-AP + yohimbine decreased MST to 7.4 minutes. Mean total recovery time (MTRT; time from xylazine injection until normal behavior, including eating and drinking) was not significantly (P = greater than 0.05) decreased from control values by any of the antagonists tested. The combination of 4-AP + yohimbine decreased MST in animals given a 3X overdose of xylazine (0.6 mg/kg) from 124 minutes (control) to 30.3 min. The MTRT was not significantly (P greater than 0.05) decreased from control values. Two animals given a 5X overdose of xylazine (1 mg/kg) and then given 4-AP + yohimbine had a MST of 32.5 minutes and a MTRT of 3.7 hours. The combination of 4-AP + yohimbine produced marked antagonism of xylazine sedation in cattle. The combination of antagonists may prove to be useful for the arousal of animals sedated with xylazine alone or with a combination of sedatives including xylazine.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002417:Cattle / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects; D013843:Thiazines / Q000037:antagonists & inhibitors*; D014991:Xylazine / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D015016:Yohimbine / Q000494:pharmacology*
D000631:Aminopyridines; D002317:Cardiovascular Agents; D000697:Central Nervous System Stimulants; D009467:Neuromuscular Depolarizing Agents; D013843:Thiazines; D014991:Xylazine; D015016:Yohimbine; D015761:4-Aminopyridine