Pascoe A L, Reynoldson J A
Comp Biochem Physiol C Comp Pharmacol Toxicol. 1986;83(2):413-7. doi: 10.1016/0742-8413(86)90145-3.
Intravenous amitraz caused significant hypotension and bradycardia in pentobarbitone anaesthetized guinea-pigs. Depression of blood pressure reached a plateau with a dose of 10 mg/kg but heart rate continued to fall in a dose-dependent manner, up to a fall of 90 beats per minute after a total of 160 mg/kg/min. Amitraz was then tested on spontaneously beating guinea-pig isolated atria. The maximum bath concentration approximated a blood concentration produced by 5 mg/kg amitraz in the guinea-pig (2.3 X 10(-4) M). Amitraz did not significantly shift the dose-response curve to isoprenaline or acetylcholine but antagonized histamine rate responses competitively in the presence of propranolol (2 X 10(-6) M). Propranolol unmasked a dose-dependent depressant effect of amitraz on atrial rate, an effect abolished with atropine (1 X 10(-5) M). Amitraz increased atrial force of contraction, an effect which was not seen when propranolol was present in the bath solution. Amitraz also depressed atrial rate directly, but this effect was minor in comparison to bradycardia seen in the guinea-pig. It is likely that the cardiovascular depression seen in the guinea-pig following amitraz i.v. is caused by an alteration in autonomic drive rather than a significant direct cardiac effect.
静脉注射双甲脒可使戊巴比妥麻醉的豚鼠出现显著的低血压和心动过缓。血压下降在剂量为10mg/kg时达到平台期，但心率继续以剂量依赖性方式下降，在总量为160mg/kg/min后心率下降高达每分钟90次。随后在自发搏动的豚鼠离体心房上对双甲脒进行测试。最大浴槽浓度接近豚鼠体内5mg/kg双甲脒产生的血药浓度（2.3×10⁻⁴M）。双甲脒未显著改变对异丙肾上腺素或乙酰胆碱的剂量反应曲线，但在普萘洛尔（2×10⁻⁶M）存在的情况下竞争性拮抗组胺引起的心率反应。普萘洛尔揭示了双甲脒对心房率的剂量依赖性抑制作用，阿托品（1×10⁻⁵M）可消除该作用。双甲脒增加心房收缩力，当浴槽溶液中存在普萘洛尔时未观察到这种作用。双甲脒也直接抑制心房率，但与豚鼠中观察到的心动过缓相比，这种作用较小。静脉注射双甲脒后豚鼠出现的心血管抑制可能是由自主神经驱动的改变引起的，而非显著的直接心脏作用。
