PHARMACOLOGICAL STUDIES ON PRESYNAPTIC INHIBITION
PHARMACOLOGICAL STUDIES ON PRESYNAPTIC INHIBITION
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DOI：
10.1113/jphysiol.1963.sp007205
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发表时间：
1963-01-01
影响因子：
5.5
通讯作者：
SCHMIDT, R
中科院分区：
文献类型：
--
作者：
ECCLES, JC;WILLIS, WD;SCHMIDT, R
对几类药物对突触前抑制作用的研究。采用的主要方法是突触前抑制单突触反射，和记录的初级传入纤维的去极化显示无论是背根电位（DRPs）或P波从脊髓背。药物通过静脉注射或脊髓局部应用给药。所有类型的突触前抑制似乎具有相同的药理学性质，并且所有报告的药理学作用都是可逆的。中剂量戊巴比妥钠（Nembutal）可延长和增加DRP、P波和单突触反射的突触前抑制。随着剂量的增加，DRP和P波进一步减慢并逐渐减少。硫戊醛钠和氯醛糖的作用相似。士的宁对突触后抑制有特异性的抑制作用，而对突触前抑制作用则有增强作用。这种效应可能是由于增强的传输沿着负责突触前抑制的多突触通路。印防己毒素抑制突触前抑制，但对突触后抑制无效。甚至在亚惊厥剂量下，它也能减少单突触反射的突触前抑制以及DRP和P波的大小，但即使是最大剂量也不能消除突触前抑制。戊巴比妥钠和印防己毒素对突触前抑制有拮抗作用。与印防己毒素类似，Metrazol（戊四唑）和bemegride（NP 13）对突触前抑制作用不一致，但对突触后抑制作用不受抑制。作用于胆碱能突触的各种药物对突触前抑制没有作用，即二氢-[β]-赤藓定、Flaxedil（三碘化没食子胺）、艾司氯胺酮、焦磷酸四乙酯和尼古丁。当中性氨基酸GABA和3-氨基丙磺酸局部应用于脊髓时，DRPs和P波降低，同时DRPs增加，这可能表明初级传入纤维的中央终末已被去极化。本文指出，许多对士的宁有抵抗作用的中枢抑制现象可能是突触前抑制的结果。它的结论是，印防己毒素的行为，特别是通过抑制负责突触前抑制的突触递质的行动。的可能性进行了讨论，印防己毒素的惊厥作用是完全归因于突触前抑制的抑郁症。
An investigation made into the action of several classes of drugs on presynaptic inhibition. The chief methods employed were the presynaptic inhibition of monosynaptic reflexes, and the recording of the depolarization of primary afferent fibres as displayed either by the dorsal-root potentials (DRPs) or the P waves from the cord dorsum. Drugs were administered either by intravenous injection or local application to the spinal cord. All types of presynaptic inhibition appeared to have the same pharmacological properties and all the pharmacological actions reported were reversible. Pentobarbl-tone aodium (Nembutal) in moderate dosage prolonged and increased the DRPs, the P waves and the presynaptic inhibition of monosynaptic reflexes. With larger doses the DRPs and P waves were further slowed and progressively diminished. Thiamylal sodium and chloralose had a similar action. In contrast to its specific depressant action on post-synaptic inhibition, strychnine usually increased presynaptic inhibition. This effect probably is due to enhanced transmission along the poly-synaptic pathways responsible for presynaptic inhibition. Picrotoxin depressed presynaptic inhibition but was ineffective on post-synaptic inhibition. Already even in subconvulslve doses it diminished the presynaptic inhibition of monosynaptic reflexes and the sizes of the DRPs and P waves, but even the largest doses failed to abolish presynaptic inhibition. Pentobarbitone sodium and picrotoxin acted antagonistically on presynaptic inhibition. There was no consistent depressant action on presynaptic inhibition of 2 other convulsant drugs, Metrazol (pentylenetetrazol) and bemegride (NP 13) that resembled picrotoxin in not depressing post-synaptic inhibition. Various drugs acting on cholinergic synapses had no action on presynaptic inhibition, viz. dihydro-[beta]-erythroidine, Flaxedil (gallamine triethiodide), eserine, tetraethyl pyrophosphate and nicotine. When applied topically to the spinal cord the neutral amino acids GABA and 3-amino-l-propanesulphonic acid depressed DRPs and P waves and at the same time increased the DRPs, which may indicate that the central terminals of the primary afferent fibres had been depolarized. In the dicussion it is pointed out that many of the central inhibitory phenomena resistant to strychnine are probably attributable to presynaptic inhibition. It is concluded that picrotoxin acts specifically by depressing the transmitter action at the synapses responsible for presynaptic inhibition. The possibility is discussed that the convulsant action of picrotoxin is attributable solely to the depression of presynaptic inhibition.