Biomedical subjects

Y Mizuki

Publications and source records attributed to Y Mizuki.

At least 55 records · Page 3Linked to original sources

PubMed1991

Effects of indeloxazine hydrochloride on sleep in normal humans.

The effects of 40 mg of indeloxazine hydrochloride, a cerebral metabolic enhancer, on sleep were investigated in 6 healthy male students. Polygraphic recordings were made for 8 consecutive nights on each subject. An inert placebo was given on the first 3 nights and on the 7th and 8th nights, and 40 mg of indeloxazine was administered on the 4th, 5th and 6th nights. Drug and placebo were administered orally at 21:30 h, and the recording of polysomnograms started at 22:00 h and ended at 8:00 h the next morning. The polysomnograms were evaluated by computerized automatic analysis using the interval histogram method. Indeloxazine prolonged both sleep latency and REM latency, and increased stage 1 sleep, but decreased stages 3, 4 and REM sleep. A significant increase of REM sleep was observed on the 7th and 8th recovery nights. No obvious changes were shown in the subjective assessments after administration of the drug. These results suggest that the effects of indeloxazine on sleep are similar to those of the tricyclic antidepressants. Furthermore, polysomnographic examinations might be useful in evaluating the pharmacological properties of cerebral metabolic enhancers.

Adult↗

PubMed1990

Effects of mianserin on negative symptoms in schizophrenia.

The efficacy of mianserin as a supplement in treating chronic schizophrenia was tested in 20 inpatients with schizophrenia who were receiving fixed doses of neuroleptics. Mianserin was given for six weeks with a starting dose of 60 mg/day. A brief psychiatric rating scale (BPRS) was completed before starting mianserin and thereafter BPRS scoring was carried out once weekly. The total BPRS score and the score for negative symptoms were decreased by mianserin treatment as compared to the pre-treatment values. Plasma 5-HIAA concentrations were increased after medication in both responding patients and nonresponding patients. However, the 5-HIAA values of responders were lower than those of nonresponders. Plasma HVA levels were slightly increased by mianserin in the responders. There were no significant changes in MHPG levels. These results suggest that the negative symptoms of schizophrenia may be improved by mianserin treatment.

Adult↗

PubMed1989

Effects of dilazep (Comelian) on the central purinergic system: inhibitory effects on clonidine-induced aggressive behavior.

Mice given clonidine (20-50 mg/kg i.p. and 5 micrograms i.c.v.) exhibited aggressive behavior. Dilazep as well as N6-(L-phenylisopropyl) adenosine (adenosine agonist) inhibited this behavior. Dilazep combined with N6-(L-phenylisopropyl) adenosine markedly inhibited the behavior at low doses that were without effect when given alone whereas the inhibitory effect of dilazep on the behavior was reversed by caffeine and 8-phenyltheophylline, which are adenosine antagonists. The results suggest that the inhibitory action of dilazep on clonidine-induced aggressive behavior can be substantially attributed to central purinoceptor stimulation.

Aggression↗

PubMed1989

A physiological marker for assessing anxiety level in humans: frontal midline theta activity.

The distinct theta rhythm in the frontal midline area during performance of mental tasks has been designated as Fm theta. Sixteen male university students who failed to show any appearance of Fm theta in 3 consecutive days were given diazepam 5 mg, amobarbital 80 mg, methylphenidate 15 mg and placebo, in a double-blind, crossover design. Scores were made on the state anxiety scale of STAI; EEGs were recorded before and during performance of an arithmetic addition. The test was repeated twice: before and one hr after drug administration. Fm theta appeared following the drug administration even in those who had never shown the appearance of Fm theta, and the appearance time of Fm theta increased in the following order: diazepam greater than amobarbital greater than placebo greater than methylphenidate. The scores of STAI decreased in the same order. The speed of performed tasks was increased by methylphenidate and placebo, but decreased by amobarbital and diazepam. These results suggest that relief from anxiety might be reflected in the appearance of Fm theta and that Fm theta might be a useful tool to measure the anxiety level in humans.

Adult↗

PubMed1989

Interaction of enoxacin with theophylline in rats.

Enoxacin (ENX) has been reported to raise significantly plasma levels of theophylline (TP) in humans. In order to elucidate a mechanism of this interaction, in vivo and in vitro studies were carried out in rats. Concomitant dosing of ENX with TP significantly elongated plasma elimination half-life of TP, which led to a marked increase in the maximum plasma TP level after repeated administrations of both drugs. In rats treated with ENX, urinary excretion of unchanged TP increased and that of TP metabolites comparably decreased. The pharmacokinetic analysis showed that ENX did not change renal clearance of TP and these observed effects of ENX were attributed to reduced metabolic clearance of TP. In the in vitro studies by using liver microsomes, ENX reduced the magnitude of the type II difference spectral interaction of TP with cytochrome P-448 (P-448) and the formation of TP metabolites catalyzed by P-448. These results strongly suggest that the inhibition of the TP binding to the ferric iron of P-448 leads to that of the TP metabolism. The most essential site of ENX to inhibit the TP metabolism was found to be the 4'-nitrogen atom in the 7-piperazinyl group, and the stereochemical structure of ENX was suggested to be responsible for this inhibition.

Animals↗

PubMed1988

The mode of action of bromocriptine following pretreatment with reserpine and alpha-methyl-p-tyrosine in rats.

The ability of bromocriptine (BRC), a selective dopamine D-2 receptor agonist, to induce yawning responses was studied in rats pretreated with reserpine and alpha-methyl-p-tyrosine (alpha-MPT). BRC (1 20 mg/kg IP) evoked yawning responses, which were pronounced at 2.5 mg/kg and characterized by the head moving downward. Higher doses of BRC (5 20 mg/kg) dose-dependently delayed the onset and peak time of yawning. A low dose of the selective D-1 dopamine receptor agonist SK&F38393 did not induce yawning but enhanced the BRC-induced response. Pretreatment with reserpine (1 and 5 mg/kg SC), alpha-MPT (100 and 300 mg/kg IP) and reserpine (1 mg/kg) plus alpha-MPT (100 mg/kg) was able to significantly reduce BRC-induced yawning. The inhibitory effects were prevented by a low dose of SK&F38393 (0.5 mg/kg IP). In particular, combined treatment with reserpine (5 mg/kg) and BRC (10 and 20 mg/kg) elicited upright fighting and jumping behaviors which were inhibited by haloperidol (1 mg/kg IP), a non-selective D-1 and D-2 receptor antagonist, SCH23390 (0.05 mg/kg SC). a selective D-1 receptor antagonist, or sulpiride (20 mg/kg IP), a potent D-2 receptor antagonist, and were potentiated by SK&F38393 (0.5 mg/kg). SCH23390 (0.05 mg/kg) decreased BRC-induced yawning and the apomorphine (low doses)-induced potentiation of BRC yawning, and prevented the apomorphine (high doses)-induced reduction of BRC yawning. SCH23390 also inhibited apomorphine-induced stereotypy and BRC-induced potentiation of apomorphine stereotypy.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1988

Multifocal sites of action involved in dopaminergic-cholinergic neuronal interactions in yawning.

Bromocriptine (BRC), a dopamine D-2 receptor agonist, physostigmine, an anticholinesterase agent and pilocarpine, a muscarinic cholinergic receptor agonist, produced yawning in rats, with the most effective doses being 2.5 mg/kg, 0.2 mg/kg and 4 mg/kg, respectively. BRC-induced yawning was inhibited by high doses of SK&F38393 (5 and 10 mg/kg), a selective D-1 receptor agonist. BRC or SK&F38393 alone did not induced stereotyped behaviors. However, when BRC was administered after SK&F38393 (5.0 and 10 mg/kg), stereotyped behaviors occurred; i.e., mainly sniffing at 2.5 and 5.0 mg/kg BRC, and mainly licking and biting 10 and 20 mg/kg BRC. A high dose of apomorphine (4 mg/kg IP) completely inhibited physostigmine-induced yawning (physostigmine yawning) but did not affect pilocarpine-induced yawning (pilocarpine yawning). BRC (2.5 20 mg/kg) increased physostigmine yawning in an additive fashion. Pilocarpine yawning was completely blocked by either low or high doses of BRC. The inhibitory effect of BRC on pilocarpine yawning was reversed by sulpiride (20 mg/kg). alpha-Methyl-p-tyrosine (alpha-MPT; 100 and 200 mg/kg) did not affect physostigmine yawning but diminished pilocarpine yawning. Furthermore, physostigmine (0.2 mg/kg) inhibited apomorphine (4.0 mg/kg)-induced hyperlocomotion and sniffing but not licking and biting, whereas pilocarpine (4.0 mg/kg) had the opposite effect.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1988

Automatic real-time analysis of human sleep stages by an interval histogram method.

A new interval histogram method for automatic, all-night sleep stage scoring, simulated on a digital computer, is described. The system consists of a 2-step analysis. The first step is recognition of elementary patterns in EEG, EOG and EMG, and the second step is the determination of sleep stages based on these parameters. Correlation of this method with power spectral analysis of the dominant EEG patterns during each sleep stage supported the reliability of the first step analysis. Overall agreement (89.1%) between the computer and human judges was only 3% less than the agreement (92.1%) among the scorers, indicating considerable reliability of the second step. The primary areas of disagreement that arose in the identification of sleep stages occurred with stages 1, 2 and REM. To improve scoring accuracy, the system may require epoch sequence information. The profile of the elementary parameters of the EEG signals clearly illustrated the cyclic nature of these activities throughout the night. The alpha and delta 2 waves clearly separated the awake state from sleep stages. Beta 2 can discriminate stages 1 and REM from stage 2, and the best indicator for distincting stage 1 from REM was muscle activity. Sigma and spindles were prominent during stage 2 sleep. Both delta 2 and high voltage delta waves distinguished stage 3 from stage 4. On the other hand, delta 1 was evenly distributed and seemed to be common to all sleep stages.

Adolescent↗

PubMed1988

Benzodiazepines increase tonic component of postdecapitation convulsions in mice.

The effects of benzodiazepines (BDZs) and GABA system on tonic and clonic component of postdecapitation convulsion (PDC) were studied in mice. Mice decapitated at the occipito-cervical junction, exerted biphasic convulsions, i.e., initially tonic and subsequently clonic convulsions. BDZs such as diazepam or clonazepam increased tonic and clonic components of PDC. These effects were not antagonized by Ro 15-1788, a benzodiazepine receptor antagonist. The increased tonic component was antagonized by the GABA receptor antagonists, bicuculline and picrotoxin, whereas the clonic component was augmented by them. Aminooxyacetic acid, which increases the endogenous GABA content by inhibiting the GABA-transaminase, increased the tonic component significantly; this increase was antagonized by both bicuculline and picrotoxin. Muscimol, a GABA agonist, however did not affect the tonic components but rather augmented the clonic component. Bicuculline and picrotoxin did not antagonize this effect of muscimol. These results indicate that endogenous GABA may play a crucial role in mediating the tonic component of PDC and the facilitation of this component by BDZs may also be due to the activation of GABA in the spinal cord. Furthermore, the mechanisms of the tonic component may be different from that of the clonic component.

Animals↗

PubMed1988

Effects of ceruletide on clinical symptoms and EEGS in schizophrenia.

1. The efficacy of ceruletide as a supplement in treating schizophrenics was tested by monitoring the Brief Psychiatric Rating Scale (BPRS) and the EEG. 2. Eight male inpatients with schizophrenia were administered fixed doses of neuroleptics during the study. 3. A control EEG recording and BPRS scoring were done before ceruletide administration. 4. Doses of 0.8 micrograms/kg/week of ceruletide and of placebo were given intramuscularly in a double-blind, crossover design for 3 consecutive weeks, and no treatment followed for 1 week. 5. EEG recordings and BPRS scoring were carried out once weekly. There were no significant differences in the total BPRS scores or the scores of each item between ceruletide and placebo. 6. With ceruletide treatment, the power values of the frontal EEGs increased in the whole bands but only in the first week. 7. The EEG values in the occipital area increased in alpha and beta activities slightly in the third week and markedly in the fourth week. 8. The power values in the right temporal area decreased in fast beta activity in the second and third weeks but increased in alpha activity in the third and fourth week. 9. The power of the left temporal area increased in both alpha and beta bands in the second week, and this continued to the fourth week. 10. These results suggest that treatment with ceruletide might fail to improve the symptoms of schizophrenics but does affect their EEGs, and that ceruletide may have a delayed effect.

Adult↗

PubMed1988

Effects of Neurotropin on polysomnographic patterns in normal humans.

The effects of Neurotropin, an analgesic drug, on polysomnographic patterns were investigated in 6 male healthy volunteers aged from 18 to 23 years (mean age 21.1 years). Polysomnographic recordings were made for 6 consecutive nights from each subject. An inert placebo, identical to the Neurotropin tablets, was given on the first 3 nights and on the sixth night. Forty-eight mg of Neurotropin (4 tablets containing 12 mg of Neurotropin each) was administered on the fourth and fifth nights. The drug and placebo were administered orally 30 min before starting the record of polysomnograms, i.e. around 22.00 h and continued until the natural awakening of the subjects the next morning. The polysomnographic record of the first night was discarded from the data, because of the first night effect. Neurotropin, given on the fourth night, significantly reduced total sleep time, stage 3 and percent of stage 3 as compared to those of the baseline placebo nights. Neurotropin given on the fifth night significantly decreased only total awakening time. These effects were not observed on the sixth placebo night (recovery night). As for the subjective assessments, no obvious changes were observed after administration of the drug. These results suggest that Neurotropin decreases total sleep time as well as stage 3 sleep. However, these effects are transient and unaccompanied by rebound phenomena. It is further suggested that Neurotropin seems to elevate slightly and transiently the arousal level.

Administration, Oral↗

PubMed1988

Effects of ethyl loflazepate (CM 6912) on sleep in normal humans.

The effects of 2 mg and 4 mg of ethyl loflazepate (CM 6912), a new anxiolytic benzodiazepine, on sleep were studied in 12 healthy male subjects. Polygraphic recordings were made for 6 consecutive nights from each subject. An inert placebo was given on the first 3 nights and on the sixth night, and 2 mg or 4 mg of CM 6912 was administered on the fourth and fifth nights to 6 subjects, respectively. The drug and placebo were administered orally 30 min after supper, and the record of polysomnograms started at 22:30 hr and continued until the natural awakening of the subjects the next morning. The polysomnograms were evaluated by computerized automatic analysis using the method of interval histogram. Both doses of CM 6912 increased total sleep time, and reduced sleep latency and total awakening in a dose-dependent manner. Both doses slightly decreased stage 1 sleep, significantly increased stage 2 sleep, but slightly decreased stages 3, 4 and REM sleep. These changes continued into the sixth recovery night. No obvious changes were observed in subjective assessments after administration of CM 6912. These results suggest that CM 6912 is an efficacious compound and has minimal adverse effects on sleep.

Adult↗

PubMed1988

[Effects of bifemelane on central dopaminergic and cholinergic systems in rats].

The study served to examine the effects of bifemelane on central dopaminergic-cholinergic neuronal mechanisms in rats. Bifemelane (5-20 mg/kg) evoked yawning responses, the frequency being low. Bifemelane (10 mg/kg) as well as bromocriptine (2.5 mg/kg) potentiated physostigmine (0.2 mg/kg)-, bromocriptine (2.5 mg/kg)- or apomorphine (0.1 and 0.5 mg/kg)-induced yawning but completely inhibited pilocarpine-induced yawning. Pretreatment with sulpiride (20 mg/kg) and a low dose of haloperidol (0.02 mg/kg) reversed the stimulatory effect of bifemelane on physostigmine-induced yawning and the inhibitory effect of the drug on pilocarpine-induced yawning, whereas atropine (5 mg/kg) diminished these yawning responses. SK&38393 (2.0 mg/kg), a dopamine D-1 receptor agonist, markedly potentiated bifemelane- and bromocriptine-induced yawning but inhibited physostigmine-induced yawning, and did not affect pilocarpine-induced yawning. The increased yawning responses were blocked by atropine and a low dose of haloperidol. Bifemelane (10 mg/kg) and bromocriptine (2.5 mg/kg) tended to increase apomorphine (5 mg/kg)-induced oral stereotypy, such as licking and biting, but the increase was not significant. These results suggest that the effects of bifemelane on central dopaminergic and cholinergic neurons may be similar to those of bromocriptine.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1987

Effects of age on behavioral responses to dopamine agonists in the rat.

This study served to examine the differential effects of age (rats aged 2 or 12 months) on behavioral responses induced by bromocriptine and apomorphine. Intraperitoneal (i.p.) injection of bromocriptine or apomorphine produced a lower frequency of yawning responses, in 12-month-old rats than in 2-month-old rats. Apomorphine produced a more pronounced stereotyped behavior in 12-month-old rats than in 2-month-old rats. Apomorphine, at 0.1 mg/kg administered after bromocriptine (1.0-20 mg/kg) potentiated yawning behavior. The frequency of yawning in 2-month-old rats was pronounced at 2.5 mg/kg of bromocriptine but only at 5 mg/kg 12-month-old rats. Apomorphine (0.1 mg/kg) did not produce perioral behavior in 2-month-old rats but did in 12-month-old rats. The apomorphine (1.0 mg/kg)-induced stereotypy was stimulated dose dependently by bromocriptine in 2-month-old-rats but not in 12-month-old rats. Bromocriptine did not produce this behavior when administered alone. Pretreatment of 2-month-old rats with reserpine, a catecholamine depletor, plus alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, inhibited the yawning induced by bromocriptine but potentiated that induced by apomorphine. Such treatment did not significantly alter either bromocriptine or apomorphine-induced yawning responses in 12-month-old rats. The apomorphine-induced stereotypy in 2-month-old rats was markedly potentiated by catecholamine depletion but was not affected in 12-month-old rats. These results suggest that the increasing effect on stereotypy and decreasing effects on yawning in the 12-month-old rats seem to result in an alteration of potency and of the ratio of D-2 versus D-1 receptor activity.

Aging↗

PubMed1986

The role of adenosinergic, GABAergic and benzodiazepine systems in hyperemotionality and ulcer formation in stressed rats.

The effects of benzodiazepines, GABA and adenosine on distress-induced hyperemotionality and gastric lesion formation were investigated in rats. Hyperemotionality such as struggling, vocalization and defecation evoked immediately after immobilization stress were attenuated by diazepam, adenosine or adenosine plus diazepam. Conversely, pretreatment with these drugs produced rapid and potent exacerbation of gastric lesions observed after 12 h of stress. The potent adenosine A1-receptor agonist N6-cyclohexyl adenosine (CHA) markedly inhibited the distress-evoked hyperemotional behaviors and potentiated the ulceration. gamma-Aminobutyric acid (GABA), muscimol, a GABA receptor agonist, and aminooxyacetic acid (AOAA), a GABA deaminase inhibitor, attenuated both stress-induced hyperemotionality and ulceration. The inhibitory effects of diazepam and GABA on hyperemotionality were reversed, respectively, by Ro15-1788, a benzodiazepine receptor antagonist, and bicuculline, a GABA receptor antagonist. The stimulatory effect of CHA on stress ulceration was potentiated by bicuculline but was not affected by Ro15-1788 or by picrotoxin, a chloride channel inhibitor. These results suggest that the mechanism involved in gastric lesion formation induced by immobilization stress may be different from that in hyperemotional behavior, and that the activation of GABAergic neurons may act as a central modulating factor in the hyperemotionality and ulceration induced by immobilization stress.

Adenosine↗

PubMed1986

Effects of acute and long-term treatments with thyrotropin-releasing hormone on locomotor activity and jumping behavior in mice.

The acute and chronic effects of thyrotropin-releasing hormone (TRH) on ambulation and, in combination with apomorphine, on jumping behavior were investigated in mice. A single administration of TRH (1-10 mg/kg SC) produced an initial hyperactivity in a dose-dependent manner. Following administration of TRH (1-10 mg/kg SC) for 21 successive days, the stimulatory effect on locomotion progressively increased. Haloperidol exerted a biphasic action on hyperlocomotion induced by acute and repeated TRH, i.e., stimulation at lower doses (0.01-0.02 mg/kg SC) and inhibition at higher doses (0.05-1 mg/kg SC). When TRH was administered in combination with low doses of apomorphine, locomotor activity was inhibited but jumping behavior occurred. The inhibitory effect of low doses of apomorphine on locomotion was shifted from doses of 0.1-0.25 mg/kg SC of apomorphine for acute TRH (10 mg/kg) to 0.25-0.35 mg/kg for repeated TRH (10 mg/kg), whereas the stimulatory effect of higher doses of apomorphine (0.5-1 mg/kg SC) on locomotion tended to decrease with repeated TRH. Jumping behavior induced by the combined treatment of TRH and apomorphine was proportional to the dose of TRH but exhibited an inverted-U response to the dose of apomorphine. Chronic TRH (10 mg/kg) in combination with apomorphine (0.1-1 mg/kg SC) also produced jumping behavior, but the dose-response curve for apomorphine was shifted to the right. The present results suggest that repeated treatment with TRH in mice produces hyperlocomotion, despite attenuation of both pre- and postsynaptic receptor activity, and that the inhibitory effect of repeated TRH on presynaptic receptors may be more potent than that on postsynaptic receptors.

Animals↗

PubMed1986

A treatment trial with an analog of thyrotropin-releasing hormone (DN-1417) and des-tyrosine-gamma-endorphin in schizophrenia.

Clinical prospects of an analog of thyrotropin-releasing hormone (DN-1417) and des-tyrosine-gamma-endorphin (DT gamma E) in schizophrenia were examined by using the Brief Psychiatric Rating Scale (BPRS) and the electroencephalogram (EEG). Twelve inpatients with chronic schizophrenia were administered fixed doses of neuroleptics throughout the study. Six patients were treated with DN-1417 (DN-1417 group), and the remaining 6 patients with DT gamma E (DY gamma E group). One mg/day of DN-1417 or DT gamma E was given intramuscularly for 2 consecutive weeks followed by 1 week of no drug treatment. In the DN-1417 group, both total BPRS scores and scores on hallucinatory behaviour and unusual thought content decreased in the first and third weeks. The power values of alpha and beta activities from the frontal area increased in the first and third weeks, whereas an increase in alpha activity and a decrease of high-fast beta activity from the occipital area were obtained during the study. On the other hand, the DT gamma E group failed to show either a decrease in BPRS scores or any remarkable EEG changes except for a slight decrease in beta activity. These results suggest that the positive symptoms of schizophrenia are improved by DN-1417 treatment, and that the alterations in BPRS scores coincide with changes in the frontal EEG.

Adult↗

PubMed1986

Effects of centrally acting drugs on the frontal midline theta activity in man.

The frontal midline theta activity which appears during a performance of mental tasks has been designated as Fm theta. Sixteen male university students who showed the appearance of Fm theta in 3 consecutive days were given 4 centrally acting drugs, i.e., diazepam 5 mg, amobarbital 80 mg, methylphenidate 15 mg and placebo, in a double-blind, crossover design. Scores were made on the state anxiety scale of Spielberger's State Trait Anxiety Inventory (STAI), and EEGs were recorded monopolarly before and during the performance of an arithmetic addition. The test was done twice, before and one hour after the drug administration. Placebo increased the appearance time of Fm theta, decreased the STAI scores and increased the tasks. Diazepam increased the appearance of Fm theta and decreased the state of anxiety but did not influence the amount of tasks. Amobarbital changed neither the appearance of Fm theta nor STAI scores but decreased the tasks slightly. Methylphenidate failed to influence the appearance of Fm theta but increased both the STAI scores and performed tasks. These results suggest that the appearance of Fm theta is influenced by the drugs and that the relief from anxiety might be involved in the appearance of Fm theta.

Adult↗