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It is well-known that bilateral occlusion of the carotid arteries produces cerebral ischemia in the Mongolian gerbil (1, 2). Ligation of one artery was used to produce a severe neurological deficit and a high mortality, which resembled the syndrome of middle cerebral arterial occlusion in humans (3). Bilateral carotid ligation in the gerbil is uniformly fatal because the collateral blood supply from the vertebral-basilar system is insufficient to prevent total cerebral infarction when the carotid flow is blocked (4). MCI-2016 is a new drug which has anti anoxic, EEG activating and memory retrieval effects in laboratory evaluations (5-7). The drug also stimulates the central noradrenergic mechanism (8). In addition to these phar macological properties, MCI-2016 has been reported to be effective for the treatment of cerebrovascular disease in recent clinical trials (9). In the present study, we examined the effects of MCI-2016 on cerebral ischemia produced by bilateral carotid ligation in the gerbil. Male Mongolian gerbils (60-108 g) were rapidly operated on under light ether anes thesia. Bilateral carotid arteries were ligated with great caution to avoid vagal irritation or injury which might cause hypoxia due to respiratory disturbances. After ligation, two studies which consisted of examination of survival time and assays of brain monoamine levels were performed independently. In order to determine the survival time, the behavior of animals was observed in a transparent plastic box (30 x 30 x 30 cm) until 36 hr after ligation. In another experiment, animals were sacrificed 1 hr after occlusion, and the brain was removed quickly. Norepinephrine (NE) and dopamine (DA) levels in whole brain excluding the cerebellum were determined by the slightly modified method of Feinhard et al. (10), and serotonin (5-HT) levels were determined by the method of Mefford et al. (11) by means of high-performance liquid chromatographic techniques. Drugs dissolved in saline were administered intraperitoneally 30 min before ligation. 1. Changes in survival time: After recovery from anesthesia, all gerbils (N=71) showed the stroke syndrome which consisted of hair rough-up, splayed limb position, circling and convulsions, and died within 36 hr. As shown in Table 1, the mean survival time in the control (saline) group was 2.4±0.5 hr. Although the mean survival time was slightly prolonged by pretreatment with 10 mg/kg MCI-201 6, the drug at 25 mg/kg was more effective: four animals given 25 mg/kg of MCI-2016 survived over 12 hr. Ca-hopantenate, a cerebral metabolic activator, also showed …

japanese journal of pharmacology/japanese journal of pharmacology

Effects of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016) on survival time and brain monoamine levels in bilaterally carotid-artery-ligated gerbils.