| Introduction: ONO-1078 {4-oxo-8-[P-(4-phenylbutyloxy)benzoylamino]-2-(tetrazol-5yl)-4H-l-benzopyran. hemihydrate}, a specific leukotriene antagonist, has been used for the treatment of asthma. The sulphidopeptide leukotrienes (LTs), a 5-lipoxygenase products of arachidonic acid, can produce various effects. Lines of evidence show that LIC4, LTD4 and LTE4 can be produced in the ischemic brains of patients and laboratory animals, induce brain vasospasm and increase vascular permeability. As a strong antagonist for LTC4, D4, E4, ONO-1078 have neuroprotective effect on brain ischemia injury. Recently, our laboratory has found that ONO-1078 do alleviate damage due to brain ischemia in the experimental models of middle cerebral artery occlusion, and effectively decrease brain edema and leakage of albumin induced by brain ischemia. These results suggest that ONO-1078 may have therapeutical potential for the treatment of brain ischemia. But it is necessary to explore other effects on central system before clinical use.Recent clinical trials with excitatory ammo acids N-methyl-D-aspartate (NMDA) receptor antagonists in patients with stoke have shown that these patients develop more adverse effects, particularly psychomimetic effects such as hallucinations and agitation, than normal volunteers at equivalent doses.NMDA antagonists can produce a variety of adverse neurobehavioral effects, these adverse events are particularly pronounced with NMDA antagonists (phencyclidine, ketamine, and MK-801) that have dissociative anesthetic properties and block NMDA receptor-mediated responses by binding to the cation channel of the NMDA receptor complex. Though they have neuroprotective effects for brain ischemia, they can not be used in the patients with brain ischemia. For this purpose, it is necessary for us to investigate the psychoneuropharmacological effects of ONO-1078 and assess its neurotoxicity.A multidisciplinary approach is necessary to assess neurotoxicity because of the complexity and diverse functions of the nervous system. For example, effects can be measured by neurochemical, neurophysiological and neuropathological techniques, whereas, others must be inferred from observed behavior. Some neurotoxicological data can be derived directly from humans. Neurotoxicity in humans is most commonly measured by relative noninvasive neurophysiologic and neurobehavioral methods that assess cognitive, affective, sensor, and motor function. However, it is necessary to rely on information derived from animal models. Including whole animal (in vivo) and tissue / cell culture (in vitro). Although ONO-1078 had been tested to draw some definite conclusions, it mainly focused on antiinflammation. Research on psychoneuropharmacological effects is not adequate. In this work, we examined systemically .possible psychoneuropharmacological response by methods of behavioral pharmacology.Aim: ONO-1078, at a 2-50 times higher doses than the optimum dose to treat brain ischemia damage, was used in this work. The general psychoneuropharmacological effects of ONO-1078 by using behavioralparadigms in mice were studied, which including: spontaneous locomotor activity, function of motor and coordination, learning and memory ability, activity of analgesia on pain models induced by heat or acetic acid. Possibility of potentiating effect on central depression by using sub-threshold dosage (30mg ?kg-1) of pentobarbital.MethodsStatistics results are presented as x眘. Statistical significance of difference between groups was determined by t test. Frequency data were compared using a Chi Square analysis.1. Chemicals and drugsONO-1078 (Ono Pharmaceutical Co, personal communication), caffeine monohydrate obtained from Wako Pure Chemical Industries (Osaka, Japan), diazepam injection (Jiangshu Jichuan Pharmaceutical Co. Ltd) and pethidine injection (Shenyang First Pharmaceutical Factory), scopolamine hydrobromde (Shanghai Harvest Pharmaceutical Co Ltd) were used in this work. All chemicals used were of analytic reagent grade.
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