Oka M, Kurokouchi A, Mori N, Kumashiro H, Ohno E
Department of Neuropsychiatry, 1 Hikarigaoka, Fukushima-shi, Japan.
No To Shinkei. 1991 Aug;43(8):769-73.
Liposomes (LIPO), which are concentric lipid layers alternating with aqueous compartments, have been suggested as a potential carrier for various drugs. In the previous studies, we have demonstrated that anticonvulsant drugs such as valproic acid, phenytoin, and DN-1417 (an analog of thyrotropin-releasing hormone) entrapped into LIPO exert more prominent therapeutic efficacy than parent drugs. In the present study, we examined the comparative effects of Lidocaine (LDCA) which acts as a proconvulsant as well as an anticonvulsant, and LIPO-entrapped LDCA (LDCA-L) on limbic status epilepticus originating in the amygdala (AM) of rats. LDCA (LDCA hydrochloride) was dissolved in distilled water as a vehicle at a concentration of 2.5 mg/ml or 10 mg/ml. LIPO and LDCA-L were prepared from L-alpha-phosphatidylcholine, cholesterol, and stearylamine. Status epilepticus was induced by intra-AM injection of combined dibutyryl (db)-cAMP-200 micrograms/ethylene diaminetetraacetic acid (EDTA)-67.2 micrograms through the implanted cannula. The animals were divided into 4 groups which received vehicle (n = 6), LIPO (n = 5), LDCA (n = 9), and LDCA-L (n = 10). LDCA group was subdivided into 5 mg/kg (n = 4) and 20 mg/kg (n = 5) groups. LDCA-L group was treated with 5mg/kg (n = 4) or 20mg/kg (n = 6). All drugs were intravenously given at a volume of 2ml/kg via teflon tube previously inserted into cervical vein 30 min after db-cAMP/EDTA injection. Vehicle or LIPO alone did not alter the pattern of electroclinical ictal responses produced by intra-AM injection of db-cAMP/EDTA.(ABSTRACT TRUNCATED AT 250 WORDS)
脂质体(LIPO)是由同心脂质层与水相间隔交替构成,已被认为是各种药物的潜在载体。在先前的研究中,我们已经证明,包封于脂质体中的抗惊厥药物,如丙戊酸、苯妥英和DN - 1417(促甲状腺激素释放激素类似物),比其母体药物具有更显著的治疗效果。在本研究中,我们研究了利多卡因(LDCA)作为惊厥诱发剂以及抗惊厥剂的比较效果,以及脂质体包封的利多卡因(LDCA - L)对大鼠杏仁核(AM)起源的边缘性癫痫持续状态的影响。将利多卡因(盐酸利多卡因)以2.5mg/ml或10mg/ml的浓度溶解于蒸馏水中作为溶媒。脂质体和LDCA - L由L-α-磷脂酰胆碱、胆固醇和硬脂胺制备而成。通过植入的套管向杏仁核内注射联合二丁酰(db)-环磷腺苷(cAMP)-200微克/乙二胺四乙酸(EDTA)-67.2微克诱导癫痫持续状态。将动物分为4组,分别接受溶媒(n = 6)、脂质体(n = 5)、利多卡因(n = 9)和LDCA - L(n = 10)。利多卡因组再细分为5mg/kg(n = 4)和20mg/kg(n = 5)组。LDCA - L组分别用5mg/kg(n = 4)或20mg/kg(n = 6)进行治疗。在注射db - cAMP/EDTA 30分钟后,所有药物均通过先前插入颈静脉的聚四氟乙烯管以2ml/kg的体积静脉给药。单独给予溶媒或脂质体不会改变经杏仁核内注射db - cAMP/EDTA所产生的电临床发作反应模式。(摘要截短于250字)