Biomedical subjects

Y Mizuki

Publications and source records attributed to Y Mizuki.

At least 19 recordsLinked to original sources

PubMed1998

Anxiolytic effects of low-dose clomipramine in highly anxious healthy volunteers assessed by frontal midline theta activity.

1. The appearance of Fm theta, the distinct EEG theta rhythm in the frontal midline area during performance of a mental task, reflects relief from anxiety in humans. 2. In the present study, the anxiolytic effects of low-dose clomipramine were examined by monitoring the Fm theta amount, the STAI scores and the plasma 5-HIAA concentration in 24 male university students with (Fm theta group, n = 12) and without (non-Fm theta group, n = 12) Fm theta. 3. Subjects were given placebo, 10 mg and 30 mg clomipramine in a double-blind crossover design. Blood samples were obtained, STAI scores were determined, and EEGs were recorded before and during the performance of an arithmetic addition task. The test was repeated twice: before and 3 hrs after drug administration. 4. In the non-Fm theta group, 10 mg clomipramine decreased the 5-HIAA concentration and state anxiety scores but increased the Fm theta amount, while 30 mg clomipramine slightly increased only the Fm theta amount. However, there were no differences in these items before and after clomipramine administration in the Fm theta group. 5. These results suggest that low doses of clomipramine such as 10 mg may exert anxiolytic effects during the acute phase of treatment in highly anxious humans.

Adult↗

PubMed1998

Modification of cataleptic responses to dopamine receptor antagonists after withdrawal from chronic cocaine or cocaine plus dopamine antagonist administration.

1. In mice pretreated chronically with cocaine (indirect dopamine agonist: 10 mg/kg, s.c. on alternating days for 15 days), haloperidol (dopamine D2 antagonist: 0.3 mg/kg i.p.) exerted an enhanced cataleptic response, but SCH23390 (dopamine D1 antagonist: 0.3 mg/kg i.p.) produced an attenuated response at 24 h, which converted to a supernormal response, when it was administered 15-60 days after withdrawal from cocaine. 2. A challenge dose of SCH23390 exhibited enhanced catalepsy when given 15 days, but not at 24 h, after the last pretreatment dose of SCH23390 (0.1-1.0 mg/kg s.c.). In contrast, haloperidol catalepsy was not affected by the SCH23390 pretreatment. 3. However, in animals chronically pretreated with haloperidol (0.1-1.0 mg/kg s.c.), a challenge dose of SCH23390 as well as haloperidol exhibited attenuated cataleptic effects at 24 h and normal cataleptic responses at 15 days after the last dose of the pretreatment regimen. 4. Challenge doses of haloperidol or SCH23390 given to mice 24 h after chronic cocaine pretreatment produced enhanced and attenuated cataleptic responses, respectively; however, these responses were no longer produced when haloperidol or SCH23390 was given to mice pretreated chronically with a combination of cocaine and either haloperidol or SCH23390. 5. The enhanced catalepsy produced by a challenge dose of SCH23390 (15-60 days after chronic cocaine) was further potentiated when it was administered to animals that had been pretreated chronically with a combination of SCH23390 and cocaine, but was antagonized in animals pretreated chronically with haloperidol and cocaine. In contrast, the degree of enhanced cataleptic responses produced by a challenge dose of haloperidol 30-60 days after pretreatment chronically with a combination of cocaine + SCH23390 was similar to that seen after chronic cocaine alone. However, this enhanced response was antagonized in animals that had been pretreated chronically with the combination of cocaine + haloperidol. 6. The results suggest that the coadministration of SCH23390 with cocaine was able to block indirectly dopamine D2 receptor inhibition (subsensitivity) induced during the early withdrawal period from chronic cocaine, despite the fact that by itself SCH23390 did not have an effect on haloperidol catalepsy. Accordingly, the stimulatory effects of dopamine D2 receptors by a single administration of cocaine may be mediated mainly by an indirect stimulation of dopamine D2 receptor function via its D1 receptor stimulating action. 7. The coadministration of SCH23390 with cocaine rather aggravate the subsensitive effect of dopamine D1 receptors (increased SCH23390 catalepsy) produced during long-term withdrawal period from chronic cocaine, but did not affect that of the dopamine D2 receptor. On the other hand, the coadministration of haloperidol with cocaine normalized both D1 and D2 receptor subsensitive effect. 8. These result suggest that a single administration of SCH23390 or haloperidol after long-term withdrawal periods from chronic cocaine may not be effective as antipsychotic drugs because of further aggravation of suppressive behaviors. These results also provide evidence that D2 receptor antagonists may be more effective as antipsychotic drugs than dopamine D1 receptor antagonist, since the coadministration of haloperidol with cocaine normalized the abnormal behaviors seen during early and long-term withdrawal periods from chronic cocaine.

Animals↗

PubMed1998

A polysomnographic study of sleep patterns in normal humans with low- or high-anxiety personality traits.

To clarify the effects of anxiety-related personality traits on sleep patterns, polysomnographic examinations (PSG) were performed over 4 consecutive nights on normal humans who tested within the low- or high-anxiety ranges. The subjects consisted of two groups of six male university students who scored either less than 45 points (low-anxiety group) or more than 55 points (high-anxiety group) on the Spielberger's State Trait Anxiety Inventory. Compared to the levels of sleep change in the high-anxiety group, the low-anxiety group exhibited a greater change in REM sleep and stage 2 sleep. The REM sleep in the low-anxiety group was shorter on the first and second nights compared to the third and fourth nights, and the stage 2 sleep was longer on the first night than on the remaining three nights. Thus, the low-anxiety group showed a first-night effect followed by partial recovery on the second night, while the high-anxiety group exhibited no obvious first-night effect. These results suggest that there is a difference in sleep patterns, assessed by consecutive PSG, between those with low- and high-anxiety traits, and that anxiety-related personality traits attenuate the occurrence of the first-night effect, reflecting a lower adaptability to a novel environment.

Adult↗

PubMed1997

Dopaminergic and cholinergic interaction in cataleptic responses in mice.

The cataleptogenic effects of haloperidol, a dopamine D2 receptor antagonist; SCH23390, a D1 receptor antagonist; physostigmine, a cholinesterase inhibitor; and pilocarpine, a muscarinic M1 receptor agonist, were challenged by pretreatment of mice with SKF38393, a dopamine D1 receptor agonist; apomorphine, a dopamine D1/D2 receptor agonist (mainly D2 receptor); pirenzepine, a muscarinic M1 receptor antagonist; and scopolamine, a muscarinic M1/M2 receptor antagonist. The effect of physostigmine and pilocarpine on haloperidol and SCH23390 cataleptic responses was also examined. Each of the challenging agents blocked one or more of the cataleptogenic agents, but only scopolamine blocked all four. Pirenzepine blocked cataleptic responses induced by SCH23390 and pilocarpine, but not those by haloperidol and physostigmine. The results of this study suggest that the action of physostigmine (endogenous acetylcholine) on M2 receptors might be more potent than that on muscarinic M1 receptors. A further interesting observation was that the haloperidol-induced catalepsy was enhanced by physostigmine pretreatment, but not by pilocarpine pretreatment, whereas the SCH23390-induced catalepsy showed the opposite spectrum of enhancement by the two cholinergic agonists. We conclude that, although the four cataleptogenic agents act via the dopaminergic-cholinergic systems, their pharmacological differences may be due largely to the different receptor subtypes that are involved in the mediation of catalepsy produced by each agent. Thus, dopamine receptors not only influence the cholinergic muscarinic receptors, but muscarinic M1 and M2 receptors also might mediate dopamine D1 and D2 receptor responses, respectively. The results suggest that there are, at the least, relationships between muscarinic M1 receptors and dopaminergic D1 receptors, and between muscarinic M2 receptors and dopaminergic D2 receptors. Dopamine D1 and D2 receptors may interact in a synergistic fashion on dopaminergic systems, but act independently of each other in influencing other system such as cholinergic neurons.

Animals↗

PubMed1997

Differential effects of dopaminergic drugs on anxiety and arousal in healthy volunteers with high and low anxiety.

1. The appearance of frontal midline theta activity (Fm theta), the distinct EEG theta rhythm in the frontal midline area during performance of a mental task, indicates relief from anxiety in humans. 2. The authors examined the effects of bromocriptine and sulpiride on anxiety and arousal in 24 male university students with (Fm theta group, n = 12) and without (non-Fm theta group, n = 12) Fm theta. Subjects were given placebo, 2.5 mg bromocriptine and 100 mg sulpiride in a double-blind crossover design. 3. Blood samples were obtained, STAI scores were determined, and EEGs were recorded before and during the performance of an arithmetic addition task. The test was repeated twice: before and 1 hr after drug administration. 4. Bromocriptine reduced the HVA concentration in both groups; sulpiride caused an increase in both groups. In the Fm theta group, bromocriptine did not alter the appearance time of Fm theta, the state anxiety score or the task performance; sulpiride increased the Fm theta amount and reduced the state anxiety but did not affect the task performance. In the non-Fm theta group, bromocriptine increased the Fm theta duration and reduced the state anxiety score but did not influence the task performance, while sulpiride reduced Fm theta and increased the state anxiety but had no effect on the task performance. 5. These results suggest that the sensitivity of presynaptic D2 receptors is higher in high-anxiety subjects compared with low-anxiety subjects, and that anxiolytic effects in high-anxiety humans and those in low-anxiety humans may be caused by decreased and increased DA activity, respectively. In addition, the stimulation of DA function may cause anxiogenic effects in high-anxiety individuals.

Adult↗

PubMed1997

Simultaneous enantiomeric determination of a gastroprokinetic agent mosapride citrate and its metabolite in plasma using alpha 1-acid glycoprotein HPLC column.

Mosapride citrate, a novel benzamide-type gastroprokinetic agent, is clinically prescribed as a racemate and is metabolized to its des-4-fluorobenzyl structure (M-1). In order to analyze simultaneously the enantiomers of mosapride and M-1 in plasma, a simple and reproducible high-performance liquid chromatographic (HPLC) method has been developed. The enantiomeric separation and determination were successfully achieved using an alpha 1-acid glycoprotein column and gradient elution with a fluorimetric detection (excitation 314 nm/emission 352 nm). Both enantiomers of mosapride and M-1 were well separated between 20 and 22 min at pH 4.4 and between 4 and 7 min at pH 5.0, respectively. Accurate determinations are possible in the concentration ranges of 10-5000 ng ml-1 for mosapride enantiomers and 50-5000 ng ml-1 for M-1 enantiomers. The intra- and inter-day coefficients of variation are satisfactory for the pharmacokinetic study of mosapride.

Administration, Oral↗

PubMed1997

Vitamin B12 treatment for delayed sleep phase syndrome: a multi-center double-blind study.

The active form of vitamin B12 (methylcobalamin) has been reported to be effective on sleep-wake rhythm disorders. Previous studies, however, were performed under open trial, and the effect of vitamin B12 has not been properly evaluated. The aim of this double-blind study was to investigate the efficacy of methylcobalamin on delayed sleep phase syndrome (DSPS). Methylcobalamin (3 mg/day) or placebo was administered for 4 weeks. The subjects were 50 patients with DSPS aged 13-55 years (26.8 +/- 1.3), 27 of whom received the active drug while 23 received the placebo. No significant differences were observed between the 2 groups in subjective evaluations of mood or drowsiness during the daytime or in night sleep by sleep-log evaluation. These results indicate that 3 mg methylcobalamin administered over 4 weeks is not an effective treatment for DSPS.

Adolescent↗

PubMed1996

Effects of chronic methamphetamine on SCH23390- or haloperidol-induced catalepsy, and effects of coadministration of SCH23390 or haloperidol in mice.

The influence of chronic treatment of mice with methamphetamine, an indirect dopamine agonist, on the cataleptic effects of R-(+)-chloro-2,3,4,5,-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin -7ol hydrochloride (SCH23390), a D1 receptor agonist, or haloperidol, a mainly D2 antagonist, was investigated. Once every other day treatment with 3 mg/kg SC methamphetamine for 15 days resulted in an increase in the catalepsy produced by haloperidol (0.3 mg/kg IP) (haloperidol catalepsy), but in a decrease in the catalepsy produced by SCH23390 (0.3 mg/kg IP) (SCH23390 catalepsy), 24 h and 7 days after withdrawal of methamphetamine. These effects of chronic methamphetamine were antagonized by coadministration of either SCH23390 (0.5 mg/kg SC) or haloperidol (1.0 mg/kg SC). These results suggest that the decreased responsiveness to SCH23390 in chronic methamphetamine-pretreated mice results from a supersensitivity of D1 receptors, and that the increased responsiveness to haloperidol catalepsy results from a subsensitivity of D2 receptors. The attenuated response to SCH23390 may be interpreted as an example of sensitization to methamphetamine, and the enhanced haloperidol response as an example of tolerance to methamphetamine, based on the development of supersensitivity and subsensitivity of D1 and D2 receptors, respectively, after chronic methamphetamine administration. Furthermore, it is suggested that coadministration of either SCH23390 or haloperidol could prevent the development of D1 receptor supersensitivity and D2 receptor subsensitivity induced by chronic methamphetamine.

Animals↗

PubMed1996

Differential effects of noradrenergic drugs on anxiety and arousal in healthy volunteers with high and low anxiety.

1. The appearance of frontal midline theta activity (Fm theta), the distinct EEG theta rhythm in the frontal midline area during performance of a mental task, indicates relief from anxiety in humans. 2. The authors investigated the effects of clonidine and yohimbine on anxiety and arousal in 24 male university students with (Fm theta group, n = 12) and without (non-Fm theta group, n = 12) Fm theta. Subjects received placebo, 0.15 mg clonidine and 15 mg yohimbine in a double-blind crossover design. 3. Blood samples were obtained, state-trait anxiety inventory (STAI) scores were determined, and EEGs were recorded before and during the performance of an arithmetic addition task. The test was repeated twice: before and 1 hr after drug administration. 4. Clonidine reduced the 3-methoxy-4-hydroxyphenylglycol (MHPG) concentration in both groups; yohimbine caused an increase in both groups. In the Fm theta group, clonidine reduced the appearance time of Fm theta and the number of task performance but did not alter the state anxiety scores; yohimbine had no effects on Fm theta or the state anxiety but increased the task performance. In the non-Fm theta group, clonidine increased the Fm theta amount and reduced the state anxiety score but did not affect task performance, while yohimbine reduced Fm theta but increased the state anxiety, the task performance and the number of errors. 5. These results suggest that changes in noradrenaline (NA) activity affect both anxiety and arousal levels in high-anxiety humans, but predominantly affect only the arousal level in low-anxiety humans.

Adrenergic Agents↗

PubMed1996

Pharmacokinetic interactions related to the chemical structures of fluoroquinolones.

Fluoroquinolone derivatives interact with methylxanthines (theophylline, caffeine) and metallic ion-containing drugs to different degrees. The rat appears to be a suitable model for predicting such interactions in man. It has been possible to determine the relationship between the chemical structure of the fluoroquinolone and the magnitude of the interaction. Fluoroquinolones with a bulky substituent at the position 8, such as sparfloxacin, lomefloxacin and fieroxacin, are less prone to interact with theophylline than those without an 8-substituent, such as enoxacin. This substituent determines the planarity of the whole fluoroquinolone molecule and the interaction tends to be more significant for planar fluoroquinolones. Furthermore, a 4'-nitrogen atom in the 7-piperazinyl group is essential for the interaction to occur. The nitrogen atom is possibly the site that binds cytochrome P-450, which catalyses theophylline metabolism. The reduction in bioavailability of fluoroquinolones by concurrent administration of aluminium hydroxide is more striking for derivatives with fewer substituents on the essential structure and on the piperazinyl group, such as norfloxacin, ciprofloxacin and enoxacin. Substitution at the 5-position diminishes the interaction, which suggests that the 5-substituent may affect the formation and/or stability of unabsorbable chelate complex which is the probable cause of the interaction. These findings are potentially useful in designing fluoroquinolones less prone to drug interactions.

Aluminum Hydroxide↗

PubMed1996

Structure-related inhibitory effect of antimicrobial enoxacin and derivatives on theophylline metabolism by rat liver microsomes.

Enoxacin, an antimicrobial fluoroquinolone with a 7-piperazinyl-1, 8-naphthyridine skeleton, is a potent inhibitor of cytochrome P-450-mediated theophylline metabolism. The present study was designed to clarify, using seven enoxacin derivatives, the molecular characteristics of the fluoroquinolone responsible for the inhibition. Three derivatives with methyl-substituted 7-piperazine rings inhibited rat liver microsomal theophylline metabolism to 1,3-dimethyluric acid to an extent similar to that of enoxacin (50% inhibitory concentrations [IC50s] = 0.39 to 0.48 mM). 7-Piperazinyl-quinoline derivatives, 8-hydroenoxacin (8-Hy) and 1-cyclopropyl-8-fluoroenoxacin (8-F1), which have a hydrogen and a fluorine at position 8, respectively, more weakly inhibited metabolite formation (IC50s = 0.88 and 1.29 mM, respectively). Little inhibition (IC50 > 2 mM) was observed in those with 3'-carbonyl and 4'-N-acetyl groups on the piperazine rings. The substrate-induced difference spectra demonstrated that the affinities of enoxacin, 8-Hy, and 8-F1 to cytochrome P-450 were parallel with their inhibitory activities. The substituent at position 8 was found to determine the molecular conformations of the fluoroquinolones, and the planarity in molecular shape decreased in the same order as the inhibitory activity (enoxacin > 8-Hy > 8-F1). Moreover, the 3'-carbonyl and 4'-N-acetyl groups decreased the basicity of their vicinal 4'-nitrogen atoms when judged from their electrostatic potentials, which showed a remarkably broadened negative charge around the nitrogens. As a result, the planarity of the whole molecule and the basicity of the 4'-nitrogen atom of enoxacin are likely to be dominant factors in the inhibition of theophylline metabolism by cytochrome P-450.

Animals↗

PubMed1996

Automatic analysis of sleep spindles--assessment in one case treated with a benzodiazepine anxiolytic drug.

Wave-form analysis and detection of sleep spindles should be automatically performed to achieve objective and highly precise determination of the pattern of appearance of sleep spindles. The conditions for constructing the automatic analysis and detection are as follows: 1) it is recommended that EEGs be sampled at 500 Hz or higher intervals; 2) the digital filter with the threshold that is most appropriate for removal of artifacts should be used; 3) various conditions for the analysis and detection of wave-forms are widely used; and 4) a procedure for inspecting and reading record paper should also be included in the set-up. Taking these points into consideration, the authors developed an automatic analysis system for sleep spindles, which employs a computer. The system was applied to a case preliminarily treated with a benzodiazepine anxiolytic drug, ethyl loflazepate (CM6912). The assessment using this system revealed that the CM6912 administration induced an increase in sleep spindles, delayed frequency, and caused amplitude increases and a prolonged duration.

Anti-Anxiety Agents↗

PubMed1996

An automatic sleep-stage analysis system with off-line high-speed processing using a super mini-computer.

An automatic sleep analysis system using a super mini-computer was developed. The system improved and expanded the data processed by the mini-computer. It had the following features: 1) wave-forms were collected and analyzed at a high speed (reproduced at 10 or 20 times the speed of a data recorder) by an off-line procedure to utilize the computer resources more efficiently; 2) all information and the original wave-forms were output to a laser printer because of the lower cost and more efficient arrangement of the data; 3) various wave-form parameters were measured by wave-form analysis; 4) the application program was based on general-purpose language; and 5) wave-form reanalysis and reconstruction of the logic was easily implemented for automatic evaluation of the sleep stages. Automatic analysis of the sleep stages was impossible for 15 of 1484 periods (20 sec per period) with one of the cases analyzed, and 142 of 1484 periods had to be corrected because of erroneous identification.

Adult↗

PubMed1996

Analysis of sleep EEGs by the interval histogram method--validity of the baseline night as a control and the effect of ethyl loflazepate (CM6912).

The effects of an anxiolytic drug, ethyl loflazepate (CM6912) on sleep EEGs were investigated by the interval histogram method originally developed. EEGs were classified into each of the delta 2-beta 2 and sigma 1 wave-form parameters, and the individual frequencies were determined on the third baseline, second drug and the first recovery nights in each sleep stage. In comparison with the second baseline night, the sigma 1 waves in stage 2 sleep and the delta 1 waves in REM sleep were decreased and the alpha and sigma 1 waves in stage 3 sleep were increased on the third baseline night. In consideration of the 5% significance level and the remarkable influence of drug administration, described below, no major problems were encountered in the use of the night as a control in this experimental schedule. The main characteristics of administration of CM6912 manifested as decreases in the slow wave, increases in the fast wave, and an increase in the sigma 1 wave in sleep stages other than stage 1. These tendencies were remarkable on the second drug night and were still evident even on the recovery night. Increases in sigma 1 wave were related to increases in sleep spindles. The increases in the beta 2 wave were particularly remarkable in REM sleep.

Adult↗

PubMed1996

Intermolecular interactions of antimicrobial fluoroquinolones with purified rat liver CYP1A2 studied by proton nuclear magnetic resonance spectroscopy.

1. Binding and inhibition of antimicrobial fluoroquinolones towards liver CYP1A2 purified from 3-methylcholanthrene-treated rats were investigated using proton nuclear magnetic resonance (nmr) and phenacetin metabolism. 2. The proton nmr longitudinal relaxation rate study indicated that the paramagnetic effects of the haem iron of CYP1A2 were observed in protons of enoxacin with a 1,8-naphthyridine skeleton and its 4'-nitrogen atom on the 7-piperazine ring probably participated in specific binding to the haem iron. These data suggest a facile accessibility and strong binding of enoxacin to the active site of the enzyme. On the contrary, the binding region of norfloxacin with a quinoline skeleton could not be specified, and an 8-fluorinated derivative (AT-3970) had much lower paramagnetic effects and no specific binding region. 3. In a reconstituted CYP1A2 system, enoxacin exhibited the most potent inhibition of phenacetin O-deethylation. The metabolism was less inhibited by norfloxacin, and AT-3970 had a weak inhibitory activity. 4. The binding ability of the fluoroquinolones to the CYP1A2 active site is likely to determine their inhibitory activity against phenacetin metabolism.

Animals↗

PubMed1995

Alteration of cataleptic responses induced by dopamine receptor antagonists after chronic cocaine administration in mice.

The influence of chronic treatment of mice with cocaine, an indirect dopamine receptor agonist, on the cataleptic effects of R-(+)-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin- 7ol hydrochloride (SCH23390), a dopamine D1 receptor antagonist, or haloperidol, mainly a dopamine D2 receptor antagonist, was investigated. Mice were given cocaine (10 mg/kg s.c.) once every other day for 7 (4 injections), 15 (8 injections) or 21 (11 injections) days. The cataleptic effects of SCH23390 (0.3 mg/kg i.p.) were significantly reduced when it was given 1-7 days after the last dose of a 7- or 15-day pretreatment course of cocaine. When SCH23390 was given 14-21 days after the cocaine the cataleptic effect was increased in the 15-day, but not the 7-day, cocaine-pretreated mice. However, after a 21-day treatment with cocaine, a challenge dose of SCH 23390 given 1-3 days thereafter produced a decreased cataleptic response, but an increased response after 7-21 days. The cataleptic effects of haloperidol (o.3 mg/kg i.p.) were reduced when it was given 1-7 days after the last dose of a 7-day pretreatment, but increased 1-3 days after that of a 15-day pretreatment with cocaine (10 mg/kg s.c.) The pretreatment with cocaine for 21 days did not affect the haloperidol catalepsy during a 1- to 3-day withdrawal period. However, haloperidol catalepsy was decreased only 7 days, then reversed 14 days and gradually increased 21 days after the last injection of a 15- or 21-day pretreatment course of cocaine. These results suggest that chronic treatment with the indirect dopamine receptor agonist, cocaine, caused supersensitivity of dopamine D1 receptors (a decrease in SCH23390 catalepsy) during the early withdrawal period and subsensitivity (an increase in SCH23390 catalepsy) after a longer period of withdrawal. It was apparent that the longer the period and the higher the dose of pretreatment with cocaine, the less were the alterations in initial responses and the greater were the alterations in subsequent responses to the dopamine D1 receptor antagonists.

Animals↗

PubMed1995

Development of tolerance and reverse tolerance to haloperidol- and SCH23390-induced cataleptic effects during withdrawal periods after long-term treatment.

The development of tolerance and reverse tolerance and reverse tolerance to the cataleptic effects of selective D1 antagonist, SCH23390, and the mainly D2 antagonist, haloperidol, was investigated in mice that had been chronically treated (7 or 30 days) with haloperidol (1 mg/kg SC), SCH23390 (0.5 mg/kg SC), or saline (5 ml/kg SC). In control animals, SCH23390 (0.1-1.0 mg/kg IP) and haloperidol (0.1-1.0 mg/kg IP) produced cataleptic responses in a dose-dependent manner, although the responses had different time course profiles. SCH23390 catalepsy had a rapid onset but a short duration, whereas haloperidol catalepsy had a slower onset and longer duration. This could be due to differences in lipid solubility of the drugs, or at least pertly to an action of the drugs on different neuronal pathways. The cataleptic effects of SCH23390 (0.3 mg/kg IP) and haloperidol (0.3 mg/kg IP) were significantly reduced in mice when given 24 h, but not 72 h, after the last dose of a 7 day-pretreatment course (short-term treatment) of SCH23390. However, after long-term treatment (30 days) with SCH23390, a challenge dose of SCH23390 exhibited reverse tolerance (i.e., increased catalepsy) when given 7-21 days, but not 1-3 days, after the last injection of the SCH23390 pretreatment course. In contrast, haloperidol catalepsy was not affected by long-term SCH23390 treatment. However, after the last dose of long-term haloperidol treatment both SCH23390 and haloperidol exhibited tolerance to their cataleptic effects at 1-3 days, a normal response at 7 days, and an exaggerated response (reverse tolerance) at 15-21 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Stimulatory effect of butoctamide hydrogen succinate on REM sleep in normal humans.

1. The efficacy of butoctamide hydrogen succinate (BAHS) was compared with that of nitrazepam on the basis of the polysomnograms and the subjective assessments. 2. Twelve healthy male students were divided into three groups consisting of 4 subjects each with were administered BAHS 600 mg, nitrazepam 5 mg, and BAHS 600 mg + nitrazepam 5 mg, respectively. 3. Polygraphic recordings were made for 8 consecutive nights for each subject, and the polysomnograms were evaluated by computerized automatic analysis using the interval histogram method. 4. An inert placebo was administered on the first 3 nights and on the seventh and eighth nights, and the test article regimen was administered on the fourth, fifth and sixth nights. 5. The test articles and the placebo were administered orally at 22:30 hr, and the recording of polysomnograms was started at 23:00 hr and ended at 8:00 hr the next morning. 6. The subjects were requested to fill out the subjective assessment of sleep before falling asleep and after arising the next morning. 7. BAHS increased REM sleep and decreased stage 2 sleep significantly; however, it failed to affect stage 1, 3 or 4 sleep. 8. Nitrazepam increased significantly the total sleep time and stage 2 sleep but decreased significantly the stage 3 sleep and decreased slightly the stages 1, 4 and REM sleep. 9. The combined treatment with BAHS and nitrazepam did not alter the sleep parameters except for increasing the total sleep time. 10. No obvious changes were observed in the subjective assessments after administration of the drugs. 11. These findings suggest that BAHS results in a unique sleep pattern different from benzodiazepines, and that BAHS may be suitable for treating insomnia in elderly patients and those with drug abuse, manic-depressive illness or schizophrenia.

Adult↗