Raines D E
Department of Anaesthesia, Massachusetts General Hospital, Boston, 02114-2696, USA.
Anesthesiology. 1996 Mar;84(3):663-71. doi: 10.1097/00000542-199603000-00022.
The Meyer-Overton rule predicts that an anesthetic's potency will correlate with its oil solubility. A group of halogenated volatile compounds that disobey this rule has been characterized. These compounds do not induce anesthesia in rats at partial pressures exceeding those predicted by the Meyer-Overton rule to be anesthetic. The observation that potentiation of GABA(A) receptor responses by anesthetic and nonanesthetic halogenated volatile compounds correlates with their abilities to induce general anesthesia suggests that this receptor is involved in the mechanism of general anesthesia. However, the GABA(A) receptor is only one member of a superfamily of structurally similar ligand-gated ion channels. This study compares the actions of both anesthetic and nonanesthetic halogenated volatile compounds on another member of this super family of receptors, the nicotinic acetylcholine receptor (nAcChoR).
The actions of both anesthetic and nonanesthetic compounds on desensitization kinetics were characterized from the time-dependent binding of the fluorescent acetylcholine analogue, Dns-C6-Cho, to the nAcChoR.
At concentrations predicted by the Meyer-Overton rule to be equianesthetic, the anesthetics isoflurane and enflurane were significantly more effective than the nonanesthetics 1,2-dichlorohexafluorocyclobutane and 2, 3-dichlorooctafluorobutane in enhancing the fraction of receptors preexisting in the slow desensitized state and increasing the apparent rates of agonist-induced fast and slow desensitization.
The potencies with which anesthetic and nonanesthetic compounds enhance desensitization kinetics in the nAcChoR parallel their in vivo anesthetic potencies. These results support the use of desensitization of the nAcChoR as a mechanistic model for studies of general anesthesia and suggest that an insensitivity to nonanesthetic compounds may be a feature common to members of the superfamily of ligand-gated ion channels.
迈耶-奥弗顿法则预测麻醉药的效能与其油溶性相关。已鉴定出一组不符合该法则的卤代挥发性化合物。这些化合物在分压超过迈耶-奥弗顿法则预测的麻醉分压时，不会在大鼠中诱导麻醉。麻醉性和非麻醉性卤代挥发性化合物对GABA(A)受体反应的增强作用与其诱导全身麻醉的能力相关，这一观察结果表明该受体参与了全身麻醉机制。然而，GABA(A)受体只是结构相似的配体门控离子通道超家族中的一员。本研究比较了麻醉性和非麻醉性卤代挥发性化合物对该受体超家族的另一个成员，烟碱型乙酰胆碱受体（nAcChoR）的作用。
通过荧光乙酰胆碱类似物Dns-C6-Cho与nAcChoR的时间依赖性结合，表征麻醉性和非麻醉性化合物对脱敏动力学的作用。
在迈耶-奥弗顿法则预测为等效麻醉浓度时，麻醉药异氟烷和恩氟烷在增加处于缓慢脱敏状态的受体比例以及提高激动剂诱导的快速和缓慢脱敏的表观速率方面，比非麻醉药1,2-二氯六氟环丁烷和2,3-二氯八氟丁烷显著更有效。
麻醉性和非麻醉性化合物增强nAcChoR脱敏动力学的效能与其体内麻醉效能平行。这些结果支持将nAcChoR的脱敏作为全身麻醉研究的机制模型，并表明对非麻醉性化合物不敏感可能是配体门控离子通道超家族成员共有的特征。
