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Biomedical subjects

M Toru

Publications and source records attributed to M Toru.

At least 127 records · Page 7Linked to original sources
PubMed1983

[High dosage haloperidol reduces cataleptic response with increased noradrenaline metabolism in the rat brain areas].

The neurochemical background of clinical experiences that the patients receiving high dosage haloperidol showed no extrapyramidal side effects was investigated by using rats. Haloperidol at doses of 1, 2.5, 5, 7.5 and 10 mg/kg, ip caused a dose-dependent decrease in the duration of catalepsy. Haloperidol at a dose of 10 mg/kg induced catalepsy lasting only 20% of that by 1 mg/kg. Haloperidol decreased noradrenaline content in the frontal cortex and thalamus in a dose-dependent manner while 3-methoxy-4-hydroxyphenylglycol content showed a dose-dependent increase in the same brain areas. Thus, there is an inverse relationship between the duration of catalepsy and the ratio of 3-methoxy-4-hydroxyphenylglycol to noradrenaline in the frontal cortex or thalamus. In contrast, haloperidol caused a dose-dependent decrease in homovanillic acid and 3, 4-dihydroxyphenylacetic acid content in the striatum and mesolimbic area. These results indicate that noradrenergic hyperfunction in the frontal cortex or thalamus induced by high dosage haloperidol may reduce cataleptogenic effect of the drug via indirect stimulation of dopaminoceptive neuron in the striatum or mesolimbic area.

Animals↗
PubMed1982

Dopamine metabolism increases in post-mortem schizophrenic basal ganglia.

The dopamine-rich regions of post-mortem brains from 6 schizophrenics and 7 controls were analyzed. There were no significant changes in dopamine concentrations in basal ganglia and nucleus accumbens of schizophrenics compared with controls. Schizophrenic basal ganglia (putamen and caudate) showed significantly higher levels of homovanillic acid, and tyrosine hydroxylase activity. Among the schizophrenic patients, markedly high activity of tyrosine hydroxylase was measured in a patient diagnosed as catatonic type. He had not taken antipsychotic drugs for 3 months prior to death. In his relatives, three other schizophrenics were found to the second degree. A remarkable low level of dopamine and a high level of homovanillic acid measured indicate this case would have had an increased turnover rate of dopamine in the dopaminergic nerve terminals. Among the schizophrenic patients, there might be one group whose enzyme activity of dopamine synthesis in the brain is exceptionally high.

Adult↗
PubMed1981

Enhancement of haloperidol-induced increase in rat striatal or mesolimbic 3,4-dihydroxyphenylacetic acid and homovanillic acid by pretreatment with chronic methamphetamine.

After a drug-free period of 1 week following 2 weeks of haloperidol treatment, the increased response of striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) to a challenge dose of haloperidol was significantly reduced. Tolerance to this effect was not, however, seen in the mesolimbic system. Pretreatment of the rats with methamphetamine (MAP) for 8 days prior to chronic haloperidol significantly enhanced the DOPAC and HVA increase produced by the challenge with haloperidol in both brain areas. The reduced response of striatal DOPAC or HVA after chronic haloperidol was prevented by pretreatment with MAP. The data suggest that the long-term dopamine receptor stimulation induced by MAP may antagonize the tolerance produced by chronic haloperidol treatment.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Neuroleptic malignant syndrome-like state following a withdrawal of antiparkinsonian drugs.

A 63-year-old woman with diagnosis of Parkinson's disease developed an unusual symptom complex which consisted of extrapyramidal symptoms, disturbances of consciousness, diaphoresis, fever, and increased serum creatine phosphokinase following the discontinuation of large doses of combined antiparkinsonian drugs. After the patient's condition did not improve with the first 14 days of treatment consisting of intravenous fluids and antibiotics, a trial administration of L-dopa and carbidopa brought about definite clinical improvement. The symptoms strongly resembled neuroleptic malignant syndrome which is often a serious complication of antipsychotic drugs. The symptoms and the treatment of the present case suggest that dopaminergic hypoactivity in the brain may be an important factor in antiparkinsonian drug withdrawal syndrome and that similar neurochemical mechanisms may exist in neuroleptic malignant syndrome.

Antiparkinson Agents↗
PubMed1981

The activity of rat pineal and brain tyrosine hydroxylase during the daily cycle of light and darkness as determined by the modified 14CO2 assay method.

A previous published assay method for tyrosine hydroxylase by the evolution of 14CO2 was modified to a two-step procedure to allow reliable measurement of large numbers of samples containing low tyrosine hydroxylase activity. The reliability of the method was examined in detail. Properties of rat brain and pineal tyrosine hydroxylase solubilized with 0.2% Triton X-100 were as follows. The apparent Km values of the brain enzyme for L-tyrosine with 1 mM-(6-DL)-5,6,7,8-tetrahydro-L-erythro-biopterin (BPH4) as cofactor and for BPH4 with 62 microM-L-tyrosine as substrate were approximately 25 microM and 85 microM, respectively. The Km's for L-tyrosine with 1 mM-(6-DL)-5,6,7,8-tetrahydro-6-methylpterin (6MPH4) as cofactor and for 6MPH4 with 210 microM-L-tyrosine as substrate were 68 microM and 270 microM, respectively. The marked substrate inhibition by high concentrations of L-tyrosine was observed only when BPH4 was used as cofactor. High concentrations of BPH4 inhibited the reaction slightly. The kinetic properties of tyrosine hydroxylase in the pineal extract were similar to those of the brain enzyme, except that a Lineweaver-Burk plot of reciprocal velocity versus the reciprocal concentration of BPH4 with 62 microM-L-tyrosine as substrate deviated downward at a BPH4 concentration of about 100 microM. Analyses of the plot indicated that the peculiar kinetic property may represent either the reaction occurring at two independent sites or with two forms (6L- and 6D-isomers) of the tetrahydrobiopterin cofactor, with apparent Km for BPH4 of 23 microM and 1025 microM, respectively, or the negatively cooperative ligand binding with a Hill coefficient of 0.72. Based on the results obtained as reported above the standard assay conditions of tyrosine hydroxylase in tissue extracts were established. Using the assay method and conditions, the absence of the daily rhythmicity of tyrosine hydroxylase in rat pineal glands and three discrete brain areas was demonstrated. The findings, especially on pineal tyrosine hydroxylase, are discussed in relation to the daily change of noradrenaline turnover.

Animals↗