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Biomedical subjects

M Murasaki

Publications and source records attributed to M Murasaki.

At least 19 recordsLinked to original sources
PubMed1995

[Recent progress in development of psychotropic drugs (2)--antipsychotics].

The discovery of chlorpromazine led to rapid progress in drug therapy for schizophrenia. However, conventional neuroleptics frequently induce EPS and tardive dyskinesia in addition to the drawback of having little effect against negative symptoms. New types of atypical antipsychotics has been actively developed in Japan to overcome these drawbacks. Firstly, serotonin-dopamine antagonist (SDA) is most actively developed. Eight SDAs have been introduced into clinical trials: risperidone's trials have been finished and a NDA has been filed, Org 5222 has been dropped because of worsening of significant cases, and 6 SDAs (SM-9018, sertindole, seroquel, AD-5423, ziprasidone and olanzapine) are now under development. Secondly, OPC-14597, a unique atypical antipsychotic has been advanced to the phase 3 study, which has both DA autoreceptor-agonistic and D2-receptor blocking actions. Thirdly, we have much interest in NE-100, a selective sigma receptor antagonist which potently suppresses the phencyclidine-induced behaviors. Finally. a 5-HT3 receptor antagonist, alosetron was already dropped because it showed no antipsychotic effects, although it was introduced with great expectations. We hope that as many as possible new antipsychotics will be approved for the battle against schizophrenia.

Animals↗
PubMed1992

The future of 5-HT1A receptor agonists. (Aryl-piperazine derivatives).

At present the dominant position among anti-anxiety medications has changed from meprobamate to the benzodiazepine derivatives. In order to avoid benzodiazepine's (BZ) undesirable side effects such as impairment of psycho-motor function, memory impairment, low dose dependence and withdrawal symptoms, a third generation anxiolytic agent, buspirone, the focus of the aryl-piperazine group of anti-anxiety agents, has been introduced recently. Aryl-piperazine derivatives work as 5-HT1A receptor partial agonists and are known as serotonin normalizers. Therefore, they are expected to have not only an anxiolytic function but also an anti-depressant effect as well. A characteristic of the aryl-piperazine derivatives is that they have no sedative and muscle relaxant effects, and they do not have BZ's undesirable side-effects, especially in regard to withdrawal symptoms. However they have a rather weak anxiolytic action and a slow onset of action. Aryl-piperazine derivatives will not take the place of BZ, but the use of BZ and buspirone as bridge medications, making the most of the strong points of both, can be proposed as a way to compensate for their respective clisadvantages.

Animals↗
PubMed1992

Single- and multiple-dose pharmacokinetics of nefiracetam, a new nootropic agent, in healthy volunteers.

The pharmacokinetic profile of nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide), a new nootropic agent, was studied in healthy Japanese male volunteers. Nefiracetam was administered orally at doses of 10-200 mg in the single-dose studies, and at doses of 200 mg three times a day for seven days in the multiple-dose study. An HPLC method was used to determine the concentrations of nefiracetam in serum, urine and faecal samples. Linear kinetic behaviour was obtained after single oral administration. Serum concentrations of nefiracetam reached maximum values (Cmax) within 2 h for all dosage groups, and declined monophasically after Cmax with half-lives of 3-5 h. The area under the concentration-time curve (AUC infinity) and Cmax were linearly related to the dose. The apparent clearance (CL) values were 94.4-140.3 mL min-1. Urinary excretion of nefiracetam was independent of the administered dose, and less than 10% of the dose was recovered in urine as the unchanged form within 24 h after administration. Renal clearance (CLR) did not change significantly as dose increased from 10 to 1200 mg. Faecal excretion of nefiracetam was less than 0.1% of the dose up to 24 h after a 300 mg oral dose. Food intake delayed the absorption of nefiracetam but did not significantly modify its pharmacokinetics. No clinically significant accumulation of nefiracetam in the body was observed during and after multiple doses.

Administration, Oral↗
PubMed1991

Abuse of "BRON": a Japanese OTC cough suppressant solution containing methylephedrine, codeine, caffeine and chlorpheniramine.

1. The paper describes the mental disturbances of 44 abusive cases of "BRON," an over-the-counter (OTC) cough suppressant solution containing methylephedrine, codeine, caffeine, and chlorpheniramine. 2. Major psychiatric symptoms observed included hallucinatory-paranoid state and affective disorder. There also were groups which exhibited a combination of the two states and abuse only. 3. The hallucinatory-paranoid state group had a relatively small BRON usage amount, short usage term and few withdrawal symptoms. The affective disorder group, in contrast, had large usage amount, longer usage term, and showed significant autonomic nerve disorders during withdrawal. These tendencies were seen more clearly in the mixed state group. 4. The hallucinatory-paranoid state group showed little or no physical dependence, while that of the affective disorder group was thought to be firmly established. Thus, in the former group, methylephedrine was considered the major behavior modifying drug, while in the latter, it was thought to be codeine.

Adult↗
PubMed1989

Pharmacokinetic study of iminodibenzyl antipsychotic drugs, clocapramine and Y-516 in dog and man.

The pharmacokinetic properties of the iminodibenzyl antipsychotic drugs clocapramine (CCP, 3-chloro-5-[3-(4-carbamoyl-4-piperidino piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) and Y-516 (3-chloro-5-[3-(2-oxo-1, 2, 3, 5, 6, 7, 8, 8a-octahydroimidazo [1,2-a] pyridine-3-spiro-4'-piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) were investigated in dog and man. Dogs were administered CCP and Y-516 intravenously, intraperitoneally, and orally, and the concentrations of the parent drugs and their metabolites in the plasma and urine were determined. Half-life (t1/2) was approximately the same by all three administration routes, being approximately 5 h for CCP and 3 h for Y-516. Bioavailability following oral administration was 0.16 +/- 0.01 (mean +/- SD, n = 3) for CCP and 0.29 +/- 0.07 for Y-516. The fractions of dose absorbed following oral administration were 0.43 +/- 0.07 and 0.79 +/- 0.24, and the fractions of dose metabolized in the liver due to the first-pass effect were 0.63 +/- 0.05 and 0.63 +/- 0.04 for CCP and Y-516, respectively. Y-516 was detected in the plasma after intraperitoneal and oral administration of CCP. The ratio of the AUC of Y-516 to that of CCP was 0.06 following intraperitoneal administration and 0.40 following oral administration. This indicated that while the metabolism of CCP into Y-516 may occur partly in the liver due to the first-pass effect, it occurs mostly within the gastrointestinal tract itself or its mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Phase I study of a new antianxiety drug, buspirone.

1. A phase I study of buspirone was conducted in 7 healthy male volunteers. 2. Diazepam was selected as the control drug and administered in equipotent doses to buspirone. Dosage was initiated at 2.5mg and doubled until a maximum dosage of 20mg was attained. Subsequently, 10mg was administered once a day for three consecutive days. 3. Clinico-pharmacologically both drugs produced sleepiness/drowsiness, but dizziness, light-headed feeling and feeling of drunkenness were marked only in the diazepam group. 4. No drug-related abnormalities were observed in clinical laboratory test values, endocrinological tests and ECG. 5. On the Uchida-Kraepelin test, no change with the control values was observed under buspirone but subjects administered diazepam exhibited marked deterioration during the latter half of the test. Moreover, in the tapping test, significant impairment was observed in the diazepam group whereas buspirone had no effect. 6. On the EEG some fast waves were observed with diazepam whereas buspirone exhibited slow waves.

Buspirone↗
PubMed1989

Comparison of therapeutic efficacy of neuroses between CM6912 (ethyl loflazepate) and diazepam in a double-blind trial.

1. The therapeutic efficacy on several neuroses between CM6912 and diazepam (DZP) was comparatively investigated by means of intergroup comparison method in a double-blind trials. CM6912 was given to CM-1 group on the basis of twice daily dose of 1 mg each in the morning and evening and to CM-2 group on the basis of once daily dose of 2 mg only in the evening and DZP was given to another group on the basis of three times each dose of 2 mg. 2. As for the overall evaluation, no significant differences were found in the percentages of final global improvement rating among three groups. It resulted in "markedly improved" by 22% in CM-2 group, 18% in CM-1 group and 15% in DZP group in order, and "more than moderately improved" by 62% in CM-2 group, 56% in DZP group and 51% in CM-1 group in order. 3. As for the overall safety rating, no differences were found in the incidence of adverse reactions. 4. As for the global utility rating, it resulted in "extremely useful" by 22% in CM-2 group, 14% in CM-1 group and 8% in DZP group in order, showing significant superiority of CM-2 group to DZP group (p less than 0.05). It resulted in "more than useful" by 58% in CM-2 group, 52% in DZP group and 50% in CM-1 group in order.

Anti-Anxiety Agents↗
PubMed1988

Phase 1 study of a new antipsychotic drug, OPC-4392.

1. A phase I study of OPC-4392 (OPC), a quinolinone derivative recently developed in Japan and recognized to have an agonistic effect on dopamine autoreceptors, was performed in 7 male healthy volunteers in comparison with chlorpromazine (CPZ). 2. Clinical pharmacology The main clinical symptoms of OPC were sleepiness, weakness, fatigability, heavy headedness, disturbance of concentration, nausea, etc. The severity of these symptoms increased dose-dependently, and the upper limit dosage of OPC was considered to be 5 mg for the healthy volunteers. 3. Endocrinological research The serum prolactin level decreased dose-dependently in the OPC group, whereas it rose in the CPZ group. A significant negative correlation was recognized between the OPC-plasma level and serum prolactin level as well. 4. Psychological tests In the Kraepelin test, a decrease in the average work quantity was observed in both groups, but it was less in the OPC group. 5. Pharmacokinetic study From the pharmacokinetic parameters measured, two features were recognized: one was the slowness of Tmax (4-6 hours) and the other was the length of its biological half-life (56-88 hours). It was estimated that the plasma level of OPC-4392 would take 2 weeks to reach a steady state.

Adult↗
PubMed1986

A sporadic case of benign myoclonus epilepsy of adult onset: its clinical aspects and electroencephalographic, polygraphic study.

A sporadic case of myoclonus epilepsy of adult onset with a benign course is presented. Its clinical implications were discussed symptomatologically and nosologically. EEG findings consisted of the slowing of basic activity, characteristic polyspike and wave discharges or other paroxysmal patterns and photomyoclonic response (PMR). The PMR was well evoked by flashes of 6-21 Hz and of yellow or red color. Clinical similarities of this case to those of hereditary myoclonus epilepsy without progressive dementia and cerebellar ataxia, and pathognomonic characteristics of electrophysiological findings indicated that the myoclonic epilepsy syndrome might share basic properties, which are state-dependent, but independent of underlying neuropathology or heredity. During sleep, paroxysmal discharges with spike(s) significantly decreased in slow-wave sleep and almost recovered in REM sleep. This finding suggests that the brain stem may be responsible for the epileptogeneity in this case.

Adult↗
PubMed1983

Psychomotor status--a female case in the 34th week of pregnancy.

A case report is presented here. A 33-year-old female who had been medicated with Chinese medicine showed a typical psychomotor status which conformed to all items of Heintel's and Treiman and Delgado-Escueta's diagnostic criteria of psychomotor status. When she was 33 years old in the 34th week of pregnancy on April 11, 1981, she was found to be in an epileptic twilight state during which a delirious state and some automatisms were observed. As the incidence of automatisms gradually increased, she was finally seized with a typical psychomotor status in which automatisms were quite periodically and frequently repeated without complete recovery of consciousness between seizures. This status still continued despite an intravenous injection of diazepam and phenytoin and barely ceased with the medication of clonazepam and carbamazepine four days after the beginning of the status.

Adult↗
PubMed1983

A multicentre double-blind comparative trial of zimeldine and imipramine in primary major depressive disorders.

Zimeldine, a new antidepressant with a selective inhibition of 5-HT reuptake, was compared with imipramine in a double-blind comparative study. The trial was conducted on 95 patients with primary major depressive disorder, of endogenous character. During the 4-week study period clinical efficacy was evaluated by using the Hamilton Depression (HAM-D) scale, Beck's Inventory and global ratings. Zimeldine (100 mg b.d.) was shown to have as good an antidepressive effect as imipramine (50 mg t.d.s.) when evaluated on the HAM-D scale. Assessment of the symptom improvement on this rating scale suggested that zimeldine was more effective in improving the patient's insight of the disease. There was no significant difference between zimeldine and imipramine as assessed by a final global improvement rating scale as well as by the patient's own impression. Exploratory data analysis revealed that zimeldine was significantly more effective than imipramine in the following groups; patients over 40 years of age; patients whose initial onset of illness occurred at over 40 years; patients with a history of at least three episodes of depressive illness; patients with mild to moderate depression; and patients who had previously failed to show an appreciable response to other antidepressant treatment. Analysis of global safety ratings revealed that zimeldine is significantly safer than imipramine, with a lower incidence of adverse symptoms involving the autonomic nervous system, especially anticholinergic reactions. No significant difference was observed between the two groups with respect to abnormal laboratory reports. One zimeldine patient developed symptoms suggesting a hypersensitivity reaction (fever, skin eruption and elevation of plasma levels of transaminases), which led to the patient's withdrawal from drug treatment.

Adolescent↗
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↗
PubMed1981

Psychomotor status induced by temporal lobe encephalitis.

A case report of psychomotor status was presented. A 51-year-old male caught a cold and had a high fever at the end of September, 1979. On October 7th, he had a visual hallucination followed by a generalized seizure. After hospitalization he went through several fits of automatism. On October 15th, he was seized with automatism status in which the seizures were repeated every 25 minutes and there was no recovery of consciousness between the seizures. Although an intravenous injection of diazepam interrupted this status, on October 17th he showed subclinical seizure status on the EEG during which automatism traces were rarely found. By the medication of carbamazepine and clonazepam, he improved gradually. CT-scan revealed the disappearance of the right sylvian fissure and CSF showed findings of viral encephalitis. Consequently, he was considered to have been suffering from temporal lobe encephalitis and shown an episode of psychomotor status with automatisms and automatism traces during which typical automatism status was observed as well.

Automatism↗