Durham H D, Frank G B, Marwaha J
Can J Physiol Pharmacol. 1977 Jun;55(3):462-70. doi: 10.1139/y77-066.
The effects of haloperidol, an antipsychotic butyrophenone, on excitability and action potential production in frog's sartorius muscle fibers were studied. This drug produced a local-anestheticlike effect which developed slowly over 1 to 5 h with lower concentrations (2.7 to 5.3 X 10(-6 M) but was completely reversed by exposing the muscles to a drug-free solution. In studies with intracellular microelectrodes, evidence was obtained showing that haloperidol decreased excitability and depressed action potential production by inhibiting the specific increase in sodium conductance (gNa) which normally follows an adequate stimulus. Evidence also was obtained showing an inhibition of the secondary increase in potassium conductance (gK). Haloperidol is structurally related to meperidine and it was found that the inhibition of gNa produced by haloperidol is partially antagonized by low concentrations of naloxone (2.8 X 10(-8) and 2.8 X 10(-7) M); as was previously shown for meperidine. Thus haloperidol, like meperidine, suppresses action potential production by two mechanisms of action: one, a nonspecific local-anaestheticlike effect; and the other, a specific inhibition of gNa mediated by means of an opiate drug receptor associated with the muscle fiber membrane. Naloxone did not antagonize the effects of chlorpromazine on gNa.
研究了抗精神病药物氟哌啶醇（一种丁酰苯类药物）对青蛙缝匠肌纤维兴奋性和动作电位产生的影响。该药物产生了类似局部麻醉的效应，在较低浓度（2.7至5.3×10⁻⁶ M）下，这种效应在1至5小时内缓慢发展，但通过将肌肉暴露于无药物溶液中可完全逆转。在细胞内微电极研究中，获得的证据表明，氟哌啶醇通过抑制通常在适当刺激后出现的钠电导（gNa）的特异性增加，降低了兴奋性并抑制了动作电位的产生。还获得了证据表明钾电导（gK）的二次增加也受到抑制。氟哌啶醇在结构上与哌替啶相关，并且发现氟哌啶醇对gNa的抑制作用可被低浓度的纳洛酮（2.8×10⁻⁸和2.8×10⁻⁷ M）部分拮抗；如先前对哌替啶所显示的那样。因此，氟哌啶醇与哌替啶一样，通过两种作用机制抑制动作电位的产生：一种是类似局部麻醉的非特异性效应；另一种是通过与肌纤维膜相关的阿片类药物受体介导的对gNa的特异性抑制。纳洛酮并未拮抗氯丙嗪对gNa的作用。
