Savic I, Widén L, Stone-Elander S
Department of Clinical Neurophysiology, Karolinska Hospital, Stockholm, Sweden.
Lancet. 1991 Jan 19;337(8734):133-7. doi: 10.1016/0140-6736(91)90799-u.
To examine whether the benzodiazepine antagonist flumazenil can reverse tolerance to benzodiazepines but without precipitating withdrawal seizures, the antiepileptic effect of flumazenil itself and its ability to reverse tolerance at a dose that would leave sufficient receptors free for the binding of benzodiazepines were investigated. Electroencephalographic studies in 6 patients with partial and 6 with generalised seizures showed that flumazenil had a short (20 min) non-dose-dependent suppressant effect on epileptic discharges in those with partial seizures. Receptor occupancy studies in 12 patients showed that 1.5 mg flumazenil given intravenously occupied 55% receptors, whereas 15 mg occupied nearly all receptors. When 3 patients with partial seizures who had become tolerant to clonazepam were given 1.5 mg flumazenil, they were seizure-free for 6-21 days after the injection. The value of intermittent therapy with a benzodiazepine antagonist for preventing or reversing tolerance to benzodiazepine agonists ought to be investigated further.
为了研究苯二氮䓬拮抗剂氟马西尼能否逆转对苯二氮䓬的耐受性，同时又不引发戒断性癫痫发作，我们研究了氟马西尼自身的抗癫痫作用，以及在能留出足够受体供苯二氮䓬结合的剂量下其逆转耐受性的能力。对6例部分性癫痫患者和6例全身性癫痫患者进行的脑电图研究表明，氟马西尼对部分性癫痫患者的癫痫放电具有短暂（20分钟）的非剂量依赖性抑制作用。对12例患者进行的受体占有率研究表明，静脉注射1.5毫克氟马西尼可占据55%的受体，而15毫克则几乎占据所有受体。当3例对氯硝西泮产生耐受性的部分性癫痫患者注射1.5毫克氟马西尼后，他们在注射后6至21天无癫痫发作。苯二氮䓬拮抗剂间歇性治疗在预防或逆转对苯二氮䓬激动剂耐受性方面的价值值得进一步研究。
