Biomedical subjects
Publications and source records attributed to K Haba.
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The calcium (Ca) antagonist flunarizine hydrochloride (FNZ) has been reported to induce parkinsonism, especially in the elderly. The effects of FNZ on dopamine receptors in rat striatal membranes, especially in aged rats, were studied using radiolabeled receptor assay. Similar displacing potencies in [(3)H]spiperone bindings were exhibited for FNZ and the Ca antagonists verapamil and nicardipine. FNZ was found to directly and competitively effect D2 receptors (D2-Rs) as an antagonist, without effecting D1 receptors. Furthermore, the washing of preoccupied membranes revealed that FNZ has a long-acting potent effect on D2-Rs. The comparative study of FNZ and sulpiride in young-adult and aged rats showed that the effect of FNZ on D2-Rs was more marked in aged rats. These results might be related to FNZ-induced parkinsonism and its high incidence in the elderly.
Changes in the regional density of muscarinic-1 (M1) receptors and the effect of lisuride hydrogen maleate on these changes were studied in senescent rat brain by in vitro autoradiography. In young adult controls, M1 receptor binding was most dense in the striatum and hippocampus, followed by the cerebral cortex and amygdala. Binding to M1 receptors was markedly lower in these areas of the senescent brain compared with the young adult brain. These decreases were reversed by intraperitoneal administration of 50 micrograms/kg.day lisuride for 14 days. The present results indicate that the therapeutic efficacy of lisuride depends on normalization of not only monoamine systems but also acetylcholine systems.
The effects of bifemelane hydrochloride on changes of N-methyl-D-aspartate receptors and muscarinic cholinergic receptors were examined in the gerbil hippocampus after transient ischemia with radioactive-specific ligands. There were marked reductions in both these receptors in the gerbil hippocampus 14 days after transient ischemia, without changes in the respective affinities. Post-ischemia bifemelane treatment almost completely prevented the ischemia-induced decreases in the numbers of these receptors, and had no effect in sham-operated controls. The results of the present study suggest that this drug prevents postsynaptic dysfunction induced by transient ischemia, and may be useful in the therapy of both the chronic and the acute stage of cerebrovascular disease.
Cerebral monoaminergic neurotransmitters and their metabolites show various concentration changes in gerbils following bilateral carotid ligation. The present study evaluated the effect of chronic administrations of lisuride hydrogen maleate (lisuride) on these changes. Lisuride (0.01 mg/kg or 0.05 mg/kg) or vehicle was intraperitoneally administered to gerbils for 14 consecutive days before the induction of a 30 min ischemia by bilateral carotid ligation. Animals were sacrified immediately and the levels of dopamine, DOPAC, homovanillic acid, noradrenaline, serotonin and 5-hydroxyindoleacetic acid determined by HPLC in the striatum, cortex, hippocampus and diencephalon/midbrain. Lisuride itself had no effect on any compound determined in any region. In the carotid-ligated gerbil brain, however, lisuride corrected the reduction of dopamine in the striatum, normalized or reduced increases in the (DOPAC+homovanillic acid)/dopamine ratio in the striatum, hippocampus and diencephalon/midbrain, and increased the levels of serotonin in all four regions. The present study, together with previous reports, indicate that lisuride may interfere with ischemia-induced cerebrovascular disturbances and, in such a way, improve some pathological sequelae of cerebrovascular disease.
Changes in various neurotransmitter systems of the gerbil brain during ischemia and the effects of administration of mergocryptine, a new ergot derivative, were studied. Gerbils intraperitoneally administered 0.5 mg/kg of mergocryptine or the vehicle once a day for 14 days were used. The administration of mergocryptine to control animals had no effect on the contents of neurotransmitters or their metabolites in various regions of the brain, but it corrected abnormalities in the neurotransmitter systems caused by ischemia. These results suggest the usefulness of mergocryptine against the deleterious effects of brain ischemia.
Effects of several cerebral metabolic activators on ischemia-induced decrease in brain acetylcholine levels were studied in gerbils. Single administration of lisuride hydrogen maleate (lisuride) significantly inhibited ischemia-induced decreases in acetylcholine in the hippocampus among various regions of the brain in 46 gerbils; however, single administration of idebenone and indeloxazine hydrochloride did not affect the ischemia-induced decreases in acetylcholine. When lisuride was intraperitoneally administered to gerbils at low doses once daily for 14 days, ischemia-induced decreases in acetylcholine were inhibited dose-dependently in all the evaluated regions of the brain. The effects of lisuride were much more marked following consecutive administration than single administration. No changes in brain acetylcholine were observed following the 14-day administration of lisuride alone without induction of ischemia. These results suggest that lisuride is not only useful for treating sequelae of cerebrovascular diseases but, when administered consecutively, is also useful for preventing ischemia-induced cerebral disturbances.