| Co-Investigator(Kenkyū-buntansha) |
WATANABE Yasuo Assistant Professor, Department of Pharmacology, Tokyo Medical College, 医学部, 講師 (70183720)
MATSUDA Hiromi Assistant Professor, Department of Pharmacology, Tokyo Medical College, 医学部, 講師 (20074651)
SATO Katsuhiko Professor, Department of Pharmacology, Tokyo Medical College, 医学部, 教授 (00133372)
SALAFSKY B. Univ. of Illinois, College of Medicine at, Director P
SALAFSKY Bernard Director & Professor, University of Illinois, College of Medicine at Rockford
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| Research Abstract |
The inhibitory effects of Ca^<2+> antagonists on excessive Ca^<2+> mobilization have been studied in hippocampus and frontal cortex of fear conditioned spontaneously hypertensive rats (SHR). This hyper-mobilization of Ca^<2+> in SHR brain regions was significantly blocked by the repeated treatment with either nitrendipine (Nit), nicardipine (Nic), flunarizine (Flu)or veraparnil (Ver), as well as benzodiazepine and 5-HT_<1A> anxiolylitics, but diltiazem failed to produce inhibition (Nedrosci, Res., 1991 ; Brain Sci. Mental Dis., 1991.). These central mechanisms of Ca^<2+> antagonists can be generally explained by their modulating synaptic transmissions and also controlling excessive intracellular Ca^<2+> levels. In different brain regions, however, some hyper-K^+ induced transmissions were not affected by single administration of Nit (Neurosci. Res. Comm., 1991). Furthermore, the remarkably different pharmacological potencies between Nic and nifedipine can be seen in their inhibitory ef
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fects on Ca^<2+> influx in cultured cerebellar granule cells, and Flu also showed the strongest inhibitory effects in these cultured cells (Jpn. Pharrnacol. Ther., 1990). In this presentation, we will discuss not only the psychotropic effects of Ca^<2+> antagonists but also their therapeutic effects on motor disorder caused by a herbicide. In summarizing this recent experiment, we note that paraquat (PQ) has a similar structure to MPP^+, a metabolite of MPTP, but it has less specific toxicity to dopamine neuron, unlike MPP^+. Treatment with small dose of PQ can produce the atypical motor disordered animal model, although intraventricular administration of large dosage of this herbicide causes severe motor dysfunctions with tonic and clonic convulsions. Following intraventricularadministration of Flu, Ver and Nic, the dynamic ataxia induced by PQ was significantly improved, but these pharmacological effects were not the same. Thus the therapeufic effects of Ca^<2+> antagonists can be used in the treatment of motor dysfunctions. Less
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