Löscher W
Arch Int Pharmacodyn Ther. 1982 May;257(1):32-58.
The cardiovascular effects of GABA, sodium valproate (VPA) and inhibitors of GABA-aminotransferase (GABA-T), namely aminooxyacetic acid, gabaculine, gamma-acetylenic GABA, gamma-vinyl GABA and ethanolamine-O-sulphate (EOS), were studied in anesthetized rats, cats and dogs. All compounds were administered intravenously in dose levels previously shown as anticonvulsant active. In rats and cats, GABA (100-1000 mg/kg) caused a sustained fall of blood pressure and heart rate. A similar reaction was observed in dogs following maintenance infusion of the amino acid. The prolonged cardiovascular depression in response to GABA could be attenuated by subsequent administration of picrotoxin and bicuculline as well as by alpha-methyltyrosine, corynanthine, chlorpromazine and tripelennamine. Phentolamine, yohimbine, propranolol, vagotomy, atropine, cyproheptadine, apomorphine and haloperidol did not antagonize the cardiovascular effects of GABA. Administration of GABA-T inhibitors provoked prolonged hypotension and bradycardia, which could be partially counteracted by picrotoxin, bicuculline and, except in the case of EOS, by chlorpromazine. VPA, in high doses (300-400 mg/kg) exerted similar cardiovascular effects in rats as observed with GABA and GABA-T inhibitors. The prolonged cardiovascular depression caused by VPA could be counteracted by bicuculline and partially by chlorpromazine. Apomorphine led to a considerable potentiation of the effects of VPA. It is concluded that GABA, GABA-T inhibitors and VPA may induce cardiovascular depression at least in part by activation of GABA receptors and that the response is mediated predominantly by the central adrenergic system. Some indication was found that an interaction with peripheral histamine contributes to the cardiovascular effects of GABA.
在麻醉的大鼠、猫和狗身上研究了γ-氨基丁酸（GABA）、丙戊酸钠（VPA）以及GABA转氨酶（GABA-T）抑制剂（即氨氧基乙酸、加巴库林、γ-乙炔基GABA、γ-乙烯基GABA和乙醇胺-O-硫酸盐（EOS））对心血管系统的影响。所有化合物均以先前显示具有抗惊厥活性的剂量静脉给药。在大鼠和猫中，GABA（100 - 1000 mg/kg）导致血压和心率持续下降。在狗身上，持续输注该氨基酸后也观察到了类似反应。后续给予印防己毒素和荷包牡丹碱以及α-甲基酪氨酸、育亨宾、氯丙嗪和曲吡那敏可减轻GABA引起的长时间心血管抑制。酚妥拉明、育亨宾、普萘洛尔、迷走神经切断术、阿托品、赛庚啶、阿扑吗啡和氟哌啶醇不能拮抗GABA的心血管作用。给予GABA-T抑制剂会引发长时间的低血压和心动过缓，印防己毒素、荷包牡丹碱以及除EOS外的氯丙嗪可部分对抗这种情况。高剂量（300 - 400 mg/kg）的VPA在大鼠身上产生了与GABA和GABA-T抑制剂类似的心血管作用。VPA引起的长时间心血管抑制可被荷包牡丹碱抵消，氯丙嗪可部分抵消。阿扑吗啡导致VPA的作用显著增强。结论是，GABA、GABA-T抑制剂和VPA至少部分通过激活GABA受体诱导心血管抑制，并且这种反应主要由中枢肾上腺素能系统介导。有迹象表明，与外周组胺的相互作用促成了GABA的心血管作用。
