Nihon yakurigaku zasshi. Folia pharmacologica Japonica
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Nippon Yakurigaku Zasshi · Aug 2001
Review[Animal models and peripheral nociception tests for the study of neuropathic pain].
Neuropathic pain associated with abnormal tactile and thermal responses that are extraterritorial to the injured nerve is known to be difficult to diagnose and treat because of clinical observation of limited responsiveness to opioids and non-steroidal anti-inflammatory drugs. To reproduce the different pathological changes observed in neuropathic pain patients, several laboratory animal models have been proposed. Recent studies using such models suggest the involvement of neuronal plasticity in pain pathways through nociceptive neurons. ⋯ After nerve injury, the nociceptive responses through type I neurons, which are polymodal C-fibers and drive NK1-receptor mechanisms in spinal pain transmission, were completely lost, but without changes in type II ones, which are polymodal C-fibers and drive NMDA receptor-mechanisms, while type III ones, which are capsaicin-insensitive (possibly A-fibers) and drive NMDA-receptor mechanisms, were markedly enhanced. Such pain transmission switch mechanisms are clearly consistent with clinical effectiveness including less sensitivity to morphine and more sensitivity to NMDA-antagonists. This article also presents currently used methods for experimental neuropathic pain models.
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Nippon Yakurigaku Zasshi · Nov 2000
Review[Pharmacological aspects of mammalian hibernation: central thermoregulation factors in hibernation cycle].
Hibernation in mammalians such as hamsters is a physiological state characterized by an extreme reduction of various functions such as body temperature and metabolism. Under such severe conditions, the central nervous system (CNS) activity is maintained at a functionally responsive level. Although hibernation is an interesting behavioral state, the physiological mechanisms of the introduction to and/or the arousal from hibernation have not been clearly defined. ⋯ This result suggests that a different system may suppress the thermogenesis center in the deep hibernation phase. Interestingly, i.c.v. injected thyrotropin releasing hormone (TRH) elevated the body temperature in both hibernation phases in hamsters. These findings suggest that the central adenosine and TRH play important roles in thermoregulation and that the new thermogenesis system, activating in low-body temperature, is induced in naturally hibernating animals.
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Nippon Yakurigaku Zasshi · Oct 2000
Review[Pharmacological characteristics of perospirone hydrochloride, a novel antipsychotic agent].
It is now known that the blockade of 5-HT2 receptors can ameliorate the negative symptoms of schizophrenia and extrapyramidal side effects (EPS) associated with antipsychotic treatments. Perospirone hydrochloride (perospirone), which was identified as a novel serotonin-dopamine antagonist (SDA)-type antipsychotic agent in 1987 by Sumitomo Pharmaceuticals, possesses high affinities both for dopamine 5-HT2 and D2 receptors. Perospirone, like conventional antipsychotics, significantly inhibited various behaviors induced by dopaminergic hyperactivation. ⋯ A recent double-blind study with schizophrenia patients demonstrated that perospirone was comparative with haloperidol in improving the positive symptoms, but was significantly superior to haloperidol against the negative symptoms. Furthermore, the extrapyramidal score in patients with perospirone treatment was lower that those with haloperidol treatment. These findings suggested that perospirone acts as an antagonist both for 5-HT2 and D2 receptors and has broader clinical efficacy and lower EPS liability than haloperidol in schizophrenia treatment.
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Nippon Yakurigaku Zasshi · Aug 2000
[The effect of anti-NGF and NGF on the responses to noxious heat in mice treated with capsaicin in the neonatal period].
Unexpectedly, despite the profound loss of C-fibers in the dorsal roots of mice injected capsaicin on day 2 of life, they showed normal responses to nociceptive heat. To examine the cause of this conflicting phenomenon, we studied the effect of anti-NGF and NGF on the response to noxious heat in mice pretreated with capsaicin. Capsaicin (50 mg/kg) was injected on the 2nd day of life, and 5 days later, anti-NGF (3 microliters/g) was daily injected for 30 days. ⋯ On the other hand, the latencies of the mice treated with both capsaicin and NGF were short compared with those of the animals treated with only capsaicin. The results may be attributed to the reinforcement of the sprouting from remaining neurons. However, we must not neglect the effect of individual treatment with NGF or anti-NGF.
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Nippon Yakurigaku Zasshi · Jan 2000
Review[Target pharmacology of topiramate, a new antiepileptic drug].
Topiramate is a novel antiepileptic drug, a fructopyranose derivative. In animal studies, topiramate suppresses maximal electroshock seizures, whereas it does not exert inhibitory effects on pentylenetetrazol-induced seizures. ⋯ In clinical studies conducted overseas, topiramate has been demonstrated to be effective in the treatment of partial seizures etc. In 55 countries including UK and USA, topiramate has been already approved for the clinical use as a drug for partial seizures, while a phase III study has been planned in Japan, using patients with symptomatic localization-related epilepsies.