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Biomedical subjects

M Toru

Publications and source records attributed to M Toru.

At least 109 records · Page 6Linked to original sources
PubMed1990

[The inhibition of dopamine D1 and D2 receptors in human putamen by antipsychotic drugs].

The inhibition of 3H-SCH 23390 (D1), 3H-spiperone (D2), and 3H-YM-09151 (D2) binding to human putamen membranes by four antipsychotic drugs was studied. Two substituted benzamides, (-)-sulpiride and YM-09151, weakly inhibited specific 3H-SCH 23390 binding to D1 receptor sites. The inhibition of 3H-SCH 23390 binding by haloperidol and chlorpromazine was also weak in the 10(-8)-10(-6) M range. All four drugs potently inhibited 3H-spiperone binding, with the following rank order of potency: haloperidol greater than YM-09151 greater than (-)-sulpiride greater than chlorpromazine. 3H-YM-09151 binding was potently displaced by YM-09151 (10(-9) M) and weakly displaced by (-)-sulpiride (10(-7) M). The potency of inhibition by haloperidol and chlorpromazine was in the 10(-8) M order.

Aged↗
PubMed1989

Benzodiazepine receptors increase in post-mortem brain of chronic schizophrenics.

[3H]-Flunitrazepam (FNT) binding was measured in the post-mortem brains of 13 chronic schizophrenics and 10 controls whose mean ages and death-to-freezing intervals were the same in each group. The specific binding of [3H]-FNT to the medial frontal cortex, orbitofrontal cortex, orbital cortex, medial and inferior temporal gyri, superior temporal gyrus, cornu Ammonis 1-3 and putamen was significantly higher in schizophrenics than in controls. Specific binding to the eye movement area (frontal eye field), motor cortex, lateral occipitotemporal gyrus, dentate gyrus of the hippocampus and secondary and tertiary visual cortex did not differ in the two groups. Type 1 benzodiazepine (BZ) binding sites in the superior temporal gyrus of schizophrenics, determined from the displacement of [3H]-FNT binding using a triazolopyridazine, CL 218,872 (200 nM), were significantly higher than in the control group. The increase in type 2 BZ binding sites was not significant. Antipsychotic or benzodiazepine medication did not appear to affect the results. There were significant correlations between specific [3H]-FNT binding and concentration of GABA (positive) and of glutamic acid (negative), specific [3H]-kainic acid binding (positive), activity of tyrosine hydroxylase (positive), and substance P-like immunoreactivity (positive) in many areas of the brain. The Bmax of [3H]-spiperone binding in the putamen was also correlated positively with specific [3H]-FNT binding. These data suggest that dysfunction of BZ receptors may be involved in the pathogenesis and some symptoms of chronic schizophrenia.

Adult↗
PubMed1988

Neurotransmitters, receptors and neuropeptides in post-mortem brains of chronic schizophrenic patients.

In the analysis of post-mortem brains of 14 chronic schizophrenic patients and 10 controls, biochemical evidence of a hyperdopaminergic state was found in the basal ganglia of schizophrenics; tyrosine hydroxylase activity was increased with a concomitant increase of homovanillic acid. Unusually high tyrosine hydroxylase activity was noted in 2 schizophrenic cases. The Bmax value of 3H-spiperone binding for schizophrenics was higher than the controls. We also found increased specific binding of 3H-kainic acid to the prefrontal cortex in schizophrenics. A negative correlation existed between 3H-kainic acid binding in the medial frontal cortex, and glutamic acid content in various brain areas. Increased immunoreactivity of substance P was found in more than ten brain areas. Methionine-enkephalin was also increased in three areas of the prefrontal cortex of schizophrenics. These results suggest that the hyperdopaminergic state co-existed with glutamatergic hypofunction and increased neuropeptides in various brain areas of chronic schizophrenic patients.

Adult↗
PubMed1988

Effects of chronic treatment with trihexyphenidyl and carbamazepine alone or in combination with haloperidol on substance P content in rat brain: a possible implication of substance P in affective disorders.

To assess the roles of substance P in neurologic or psychiatric illnesses, effects of acute or chronic (40- or 80-day dietary) treatment with trihexyphenidyl and carbamazepine alone or in combination with haloperidol on substance P content were investigated in the rat brain. Either acute or chronic trihexyphenidyl administration did not alter substance P content when administered alone and did not prevent the haloperidol-induced substance P decrease in the striatum and substantia nigra when coadministered with haloperidol. Chronic dietary carbamazepine administration dose-dependently increased substance P content in the striatum and substantia nigra, but not in the raphe area, in a haloperidol-reversible manner. Carbamazepine also dose-dependently increased gamma-aminobutyric acid levels in the substantia nigra without altering the striatal dopamine turnover rate. The lack of effect of trihexyphenidyl, an anticholinergic drug used to treat antipsychotic drug-induced extrapyramidal (Parkinson) syndromes, suggests that antipsychotic drug-induced reduction in substance P content is not involved in the extrapyramidal side effects. Since the effects of carbamazepine on substance P content are identical with previously described effects of lithium, an alteration in substance P neurotransmission may be one of the neurochemical bases of common clinical and behavioral effects of carbamazepine and lithium on affective disorders.

Animals↗
PubMed1985

Haloperidol in large doses reduces the cataleptic response and increases noradrenaline metabolism in the brain of the rat.

The neurochemical basis for the clinical observation that some patients receiving a large dose of haloperidol exhibit no extrapyramidal side effects was investigated in rats. Haloperidol at doses of 1, 2.5, 5, 7.5 and 10 mg/kg (i.p.) caused a dose-dependent decrease in the duration of catalepsy. Haloperidol at a dose of 10 mg/kg induced catalepsy lasting for only 20% of that obtained with 1 mg/kg. Haloperidol decreased the content of noradrenaline in the frontal cortex and thalamus in a dose-dependent manner, while the content of 3-methoxy-4-hydroxyphenylglycol (MHPG) showed a dose-dependent increase in the same areas of the brain. Thus, there was an inverse relationship between the duration of catalepsy and the ratio of 3-methoxy-4-hydroxyphenylglycol to noradrenaline in the frontal cortex or thalamus. The concomitant administration of 20 mg/kg of phenoxybenzamine with 10 mg/kg of haloperidol induced a long-lasting catalepsy. The result may indicate that the increased metabolism of noradrenaline by large doses of haloperidol was not secondary to the blocking of dopaminergic receptors. In contrast, haloperidol caused a dose-dependent decrease in the content of homovanillic acid and 3,4-dihydroxyphenylacetic acid in the striatum and mesolimbic area. These results indicate that noradrenergic hyperfunction in the frontal cortex or thalamus induced by large doses of haloperidol may reduce the cataleptogenic effect of the drug via indirect stimulation of a dopaminoceptive neuron in the striatum or mesolimbic area.

Animals↗
PubMed1984

Increased brain serotonin metabolism during rebound sleep in sleep-deprived rats.

Adult male Wistar rats were almost totally deprived of sleep by handling for 24 hr. 5-Hydroxyindolacetic acid concentrations in the dorsal raphe nucleus area and thalamus increased by 140-180%, immediately after sleep deprivation and when the rats had a 3- or 30-min rebound sleep. The higher levels of 5-hydroxyindolacetic acid were still observed after the rats were awakening from a 4-hr sleep. The concentrations of 5-hydroxytryptamine (serotonin) decreased after sleep deprivation and increased during and after sleep, but the differences were not significant. Tryptophan accumulated in the dorsal raphe area and thalamus after sleep deprivation, and an elevated level did not return to baseline concentrations until the rats were awakening. Tryptophan hydroxylase activity did not change in the dorsal raphe area during and after sleep deprivation. These results suggest that the release and synthesis of 5-hydroxytryptamine in the dorsal raphe area and thalamus increased when the rats had a sleep pressure or a rebound sleep after total sleep deprivation. An increased transport of tryptophan into the brain may be closely involved in sleep-inducing mechanisms.

Animals↗
PubMed1984

Twenty-four hour rhythms of norepinephrine and serotonin in nucleus suprachiasmaticus, raphe nuclei, and locus coeruleus in the rat.

Twenty-four hour rhythms, at 4 h intervals, of norepinephrine (NE) and serotonin (5-HT) contents were investigated in the rat brain regions where sleep-wakefulness regulation is believed to occur: Nucleus suprachiasmaticus (SC), n. raphe dorsalis (RD) and medialis (RM), and locus coeruleus. Cosinor method of Halberg was applied to evaluate sinusoidal rhythmicity of the measured values. In the SC only NE showed a significant rhythm with a peak value at the beginning of the light period, which suggests that a NE mechanism may be involved in oscillating biological rhythms in rats. In the RD and RM, 5-HT and 5-hydroxyindoleacetic acid increased significantly during the light period. Moreover, 5-HT rhythm in the RD was maintained even under constant dark conditions, which suggests that 5-HT rhythm in the RD may be endogenous.

Animals↗
PubMed1983

Increased muscarinic cholinergic receptors in prefrontal cortices of medicated schizophrenics.

Alterations in 3H-quinuclidinyl benzilate binding sites associated with muscarinic cholinergic receptors were investigated in orbito-frontal and medial frontal cortices from 12 schizophrenics, 6 on-drug and 6 off-drug cases, and from 10 controls. Significantly lower affinities of the sites were found in both areas of schizophrenics than controls. An increase in receptor number was shown only in the orbito-frontal cortex from schizophrenics. On-drug group of schizophrenics did, however, show a significant increase in receptor number and a significant decrease in affinity in both areas, while there were no significant differences in any binding parameters of off-drug schizophrenics from controls. Also in the caudate the similar results were obtained. It is, thus, concluded that alterations in muscarinic cholinergic receptors of schizophrenic patients result from long-term medication with antimuscarinic actions.

Adult↗
PubMed1983

Increased [3H]kainic acid binding in the prefrontal cortex in schizophrenia.

[3H]Kainic acid binding sites were measured post mortem in the putamen and prefrontal cortex areas from 10 control subjects and 12 schizophrenic patients. A 25-50% increase in [3H]kainic acid binding was observed in the medial frontal (Brodmann areas 9, 10 and 46) and eye-movement areas (8), but not in the other regions of schizophrenic brains. No significant correlation between the binding and either age at death, storage of the brains, duration of illness or neuroleptics-free period was observed. These findings suggest that a dysfunction of cortical excitatory amino acidergic transmission may be involved in schizophrenia.

Aged↗
PubMed1983

Behavioral sensitization and relative hyperresponsiveness of striatal and limbic dopaminergic neurons after repeated methamphetamine treatment.

Rats were used in a study of the effects of repeated methamphetamine treatment on stereotyped behavior and striatal and limbic dopamine metabolism in response to challenge with the drug or other dopamine agonists. Repeated administration of d-methamphetamine (6 mg/kg per day for 3-14 days) produced long-term behavioral sensitization (augmented response to a challenge injection) not only to the compound (at 44-89 days after drug withdrawal) but also to apomorphine and nomifensine. Even a single injection of d-methamphetamine (6 mg/kg) enhanced the behavioral response to the drug. A challenge dose of d-methamphetamine (2 mg/kg) markedly increased dopamine turnover (lower dopamine and higher 3,4-dihydroxyphenylacetic acid levels, higher ratios of 3,4-dihydroxyphenylacetic acid over dopamine) in the striatum and mesolimbic area of the sensitized animals on day 15 of withdrawal from treatment repeated for 14 days with the drug (6 mg/kg per day). These findings demonstrate that behavioral sensitization induced by methamphetamine is accompanied by increased central dopaminergic transmission.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

A comparison of the clinical effects of timiperone, a new butyrophenone derivative, and haloperidol on schizophrenia using a double-blind technique.

The efficacy and safety of timiperone, a new butyrophenone derivative, in schizophrenia as compared with haloperidol were assessed in a multi-clinic double-blind controlled study in a total of 206 patients. The patients were given timiperone (1.0 mg/tablet) or haloperidol (1.5 mg/tablet) in a daily dose of 1--3 tablets for the first day, then up to a maximum of 12 tablets depending on symptoms for 12 weeks. Timiperone was found to be significantly superior to haloperidol in the final global improvement rating and in the general usefulness rating. In the over-all safety rating there were no statistically significant differences between the two drug treatments. With regard to analysis by stratification timiperone was superior to haloperidol in improving abnormal experiences such as hallucination and delusion as well as deficiency of initiative and blunted affect. From these results it is considered that timiperone could be superior to haloperidol in the treatment of schizophrenia.

Adolescent↗