Biomedical subjects

Y Imagawa

Publications and source records attributed to Y Imagawa.

At least 19 recordsLinked to original sources

PubMed2001

Microsatellite mapping of a susceptible locus within the HLA region for Behçet's disease using Jordanian patients.

Behçet's disease (BD) has been established to be associated with HLA-B51. However, it has not been revealed whether the HLA-B51 gene itself or another gene located near the HLA-B gene is directly involved in the pathogenesis of BD. Previously, using Japanese BD patients, our group has narrowed down a BD-causative gene to 46 kb between the MICA and HLA-B genes by means of fine mapping analysis with eight microsatellite markers distributed within a 1100 kb segment around the HLA-B gene. To know whether this mapping result is generally observed in BD of another population we have investigated repeat polymorphisms of the same microsatellite markers in Jordanian BD patients. Furthermore, we have evaluated these data by Mantel-Haenzel stratified analysis to find out a primarily associated locus for BD. As a result, HLA-B51 was found to be the most strongly and primarily associated marker. This result suggests that the pathogenic gene of BD is HLA-B51 itself, but unlikely to be other genes located in the vicinity of HLA-B.

Adolescent↗

PubMed2001

The absence of disease-specific polymorphisms within the HLA-B51 gene that is the susceptible locus for Behçet's disease.

Behçet's disease is known to be associated with HLA-B51 in many different populations. Genetic evidence supports that the susceptible gene for Behçet's disease is the HLA-B51 allele at the HLA-B locus. This study was aimed to determine the HLA-B51 nucleotide sequence variation in three Behçet's disease patients and three healthy controls in order to elucidate if any disease specific mutations or polymorphisms may exist in the HLA-B51 gene of patients. Long-range polymerase chain reaction (PCR) was first carried out to give a PCR-amplified product of 9.5 kb which was then used as a template for nested PCR to give a final amplified product of 4.2 kb. This final product containing the 1.3-kb promoter/enhancer region and the entire HLA-B gene except for a 363-bp 3' terminal end segment encoding the 3' untranslated region was subcloned by the BP cloning technique and sequenced. The sequencing results showed that all the patients possessed the HLA-B*51011 allele, and there were no differences in the exonic nucleotide sequences between the three Behçet's disease patients and the three healthy controls. The HLA-B*51011 intronic and promoter/enhancer nucleotide sequences from the three patients had 22 single nucleotide polymorphisms (SNPs), a single insertion of 6 bp and a single deletion of 2 bp. On the other hand, the three healthy controls had 24 SNPs in their intronic and promoter/enhancer regions. However, none of these polymorphisms in the patients were specific for the disease. Therefore, these results clearly demonstrate that the HLA-B exonic sequence that encodes the HLA-B51 allele is the real pathogenic factor in Behçet's disease.

5' Flanking Region↗

PubMed1999

Anxiety-like behavior in mice lacking the angiotensin II type-2 receptor.

The main biological role of angiotensin II type 2 receptor (AT2) has not been established. We made use of targeted disruption of the mouse AT2 gene to examine the role of the AT2 receptor in the central nervous system (CNS). AT2-deficient mice displayed anxiety-like behavior compared with wild-type mice. However, AT2-deficient mice showed no depressant-like activity and no change in hexobarbital-induced sleeping time as compared with findings in wild-type mice. Both noradrenergic and corticotropin-releasing factor (CRF) neuronal systems appear to be involved in this anxiety-like behavior. Diazepam, captopril (angiotensin I converting enzyme inhibitor), prazosin (alpha1 antagonist) reversed the anxiety-like behavior in these AT2-deficient mice, whereas yohimbine (alpha2 antagonist), phenylephrine (alpha1 agonist), clonidine (alpha2 agonist), isoproterenol (beta1/beta2 agonist), propranolol (beta1/beta2 antagonist) and alpha-helical CRF9-41 (CRF receptor antagonist) has no apparent effects on anxiety-like behavior in AT2-deficient mice. In addition, concentrations of plasma adrenocorticotropic hormone (ACTH) and corticosterone in AT2-deficient mice did not differ from these in wild-type mice, hence, there are probably no endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis (HPA). The amygdala appears to play an important role in many of the responses to fear and anxiety. The number of [3H]prazosin but not [125I]CRF binding sites in the amygdala was significantly reduced in AT2-deficient mice. These findings indicate that the noradrenergic system is involved in mediating the anxiety-like behavior in AT2-deficient mice.

Adrenocorticotropic Hormone↗

PubMed1997

In vitro and in vivo characterization of the dopamine D4 receptor, serotonin 5-HT2A receptor and alpha-1 adrenoceptor antagonist (R)-(+)-2-amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl] pyrrolidin-3-yl]thiazole (NRA0045).

(R)-(+)-2-Amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl]+ ++pyrrolidin-3-yl]thiazole (NRA0045), a novel thiazole derivative, has high affinities for the human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 2.54, 0.55 and 0.54 nM, respectively. NRA0045 is approximately 91-fold more potent at the dopamine D4.2 receptor, compared with human cloned dopamine D2L receptor. NRA0045 also has high affinities for the serotonin (5-HT)2A receptor (Ki = 1.92 nM) and alpha-1 adrenoceptor (Ki = 1.40 nM) but weak affinities (IC50 values are approximately 1 microM) for six other neurotransmitter receptors (adenosine1, 5-HT1A, 5-HT1C, dopamine transporter, alpha2A and alpha2A) and negligible affinities (IC50 values are over 10(-5) M) for 42 other receptors, including neurotransmitters and hormones, ion channels and second messenger systems. Locomotor hyperactivity induced by methamphetamine (1 mg/kg i.p.) in mice was dose-dependently antagonized by NRA0045 (ED50 = 0.5 mg/kg i.p. and 1.9 mg/kg p.o., respectively). Methamphetamine (10 mg/kg i.p.)-induced stereotyped behavior in mice was dose-dependently antagonized by NRA0045, whereas NRA0045 did not exceed 50% inhibition even at the highest dose given (30 mg/kg i.p.). Catalepsy was dose-dependently and significantly induced by NRA0045 in rats, whereas NRA0045 did not exceed 50% induction even at the highest dose given (30 mg/kg i.p.). Thus NRA0045 blocks behaviors associated with activation of the mesolimbic/mesocortical dopaminergic neurons more selectively than behaviors associated with nigrostriatal dopaminergic neurons. In rats, tryptamine-induced clonic seizure, a 5-HT2 receptor-mediated behavior, was also dose-dependently inhibited by NRA0045 (ED50 = 1.7 mg/kg i.p.). Norepinephrine-induced lethality is regarded as being induced through the alpha-1 adrenoceptor. NRA0045 dose-dependently antagonized norepinephrine-induced lethality in rats (ED50 = 0.2 mg/kg i.p.). Thus NRA0045 may have a unique antipsychotic activity with regard to dopamine D4 and 5-HT2A receptors and alpha-1 adrenoceptor antagonistic activities, without producing the extrapyramidal side effects.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1996

Behavioral evidence for modulation by sigma ligands of (+)MK-801-induced hyperlocomotion in monoamine-depleted mice.

The selective non-competitive N-methyl-D-aspartate (NMDA) antagonist (+)-5-methyl-10, 11-dihydro-5H-dibenzo(a, d)cyclohepten-5,10-imine maleate ((+)MK-801) led to a dose-dependent increase in locomotor activity in mice pretreated with a combination of reserpine and alpha-methyl-para-tyrosine (alpha-MT). A selective and potent sigma receptor "antagonist" NE-100 (N, N-dipropyl-2- [4-methoxy-3-(2-phenylethoxy)-phenyl]-ethylamine monohydrochloride), which did not per se affect spontaneous locomotor activity, did not prevent the locomotor stimulatory effects of (+)MK-801. Sulpiride, a dopamine D2 receptor antagonist, and clozapine, a dopamine D4 receptor antagonist, which decreased spontaneous locomotor activity, did not prevent the locomotor stimulatory effects of (+)MK-801. The sigma receptor "agonists" (+)N-allynormetazocine [(+)SKF10,047], (+)pentazocine and (+)-3-(3-hydroxyphenyl)-N-(1-propyl) piperidine [(+)3-PPP], which did not per se affect spontaneous locomotor activity, did dose-dependently enhance the hyperlocomotion induced by (+)MK-801. The enhancement of (+)MK-801-induced the hyperlocomotion by (+)SKF10,047, (+)pentazocine and (+)3-PPP was completely blocked by NE-100. The enhancement of (+)MK-801-induced hyperlocomotion by (+)pentazocine was not affected by treatment with sulpiride and clozapine. As sigma ligands can markedly attenuate NMDA antagonist-induced behavior, the major physiological role of sigma receptors in vivo might be to modulate functions of the NMDA receptor ion channel complex.

Animals↗

PubMed1996

[In vitro antibacterial activity of pazufloxacin (PZFX) against clinical isolates from infectious enteritis].

Antibacterial activity of pazufloxacin (PZFX) against 65 strains of Shigella spp., 13 strains of Salmonella spp., 7 strains of Escherichia coli, 4 strains of Vibrio parahaemolyticus, 4 strains of V. cholerae O1, 2 strains of Aeromonas spp., 4 strains of Plesionomas shigelloides and 3 strains of V. cholerae non-O1 isolated from patients of infectious enteritis and carriers was compared with that of ofloxacin (OFLX), ciprofloxacin (CPFX), tosufloxacin (TFLX) and nalidixic acid (NA). The MIC90 of PZFX against Shigella spp., Salmonella spp. and E. coli were 0.025, 0.025 and 0.025 micrograms/ml, respectively. The MIC90 of PZFX against Shigella spp. was comparable to that of CPFX, 2-fold higher than that of TFLX and 4-fold lower than that of OFLX. Against Salmonella spp., MIC90 of PZFX was comparable to TFLX and 2- to 8-fold lower than those of CPFX and OFLX. PZFX showed the highest antibacterial activity between the drugs tested. Against other species, the MIC90 values of PZFX were < or = 0.006-0.1 micrograms/ml. No NA-resistant isolates were observed. The antibacterial activity of PZFX against stocked strains (clinical isolates from Aug 1989 to Feb 1991), containing 51 strains of Shigella spp., 50 strains of Salmonella spp., 19 strains of E. coli, 12 strains of V. cholerae O1 and 13 strains of V. parahaemolyticus, was also investigated. The MIC90 of PZFX of each strains were 0.05 micrograms/ml for Shigella spp., 0.05 micrograms/ml for Salmonella spp., 0.1 micrograms/ml for E. coli, 0.0125 micrograms/ml for V. cholerae O1, 0.2 micrograms/ml for V. parahaemolyticus, respectively. As shown above, PZFX has strong antibacterial activity against isolates from infectious enteritis and this suggests the usefulness of PZFX for the treatment of these patients and carriers.

4-Quinolones↗

PubMed1995

Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor.

There are two major angiotensin II receptor isoforms, AT1 and AT2. AT1 mediates the well-known pressor and mitogenic effects of angiotensin II, but the signalling mechanism and physiological role of AT2 has not been established. Its abundant expression in fetal tissues and certain brain nuclei suggest possible roles in growth, development and neuronal functions. Here we report the unexpected finding that the targeted disruption of the mouse AT2 gene resulted in a significant increase in blood pressure and increased sensitivity to the pressor action of angiotensin II. Thus AT2 mediates a depressor effect and antagonizes the AT1-mediated pressor action of angiotensin II. In addition, disruption of the AT2 gene attenuated exploratory behaviour and lowered body temperature. Our results show that angiotensin II activates AT1 and AT2, which have mutually counteracting haemodynamic effects, and that AT2 regulates central nervous system functions, including behaviour.

Angiotensin II↗

PubMed1995

[In vitro antibacterial activity of balofloxacin (BLFX) against isolates from patients with bacterial enteritis].

In vitro antibacterial activity of balofloxacin (BLFX), a newly developed fluoroquinoline, was compared with that of norfloxacin (NFLX), ofloxacin (OFLX) and ciplofloxacin (CPFX). Bacterial strains used in this experiment were freshly isolated from patients with infectious enteritis just before BLFX therapy. The isolates were 43 strains of Vibrio cholerae O1, 1 strain of Campylobacter sp., 4 strains of Aeromonas spp., 3 strains of Plesiomonas shigelloides, 1 strain of Vibrio mimicus and 1 strain of Vibrio cholerae non-O1. MIC90 of BLFX against 43 strains of Shigella spp., 13 strains of Salmonella spp. and 9 strains of E. coli were 0.39, 0.39, 0.2 micrograms/ml, respectively. All strains of Aeromonas spp. and P. Shigelloides were inhibited by the concentrations under 0.39 and 0.05 micrograms/ml. MIC90 of BLFX, NFLX, OFLX and CPFX against a total of 79 strains were 0.39, 0.2, 0.2 and 0.05 micrograms/ml, respectively.

Anti-Infective Agents↗

PubMed1994

NE-100, a novel sigma receptor ligand: effect on phencyclidine-induced behaviors in rats, dogs and monkeys.

Phencyclidine (PCP)-induced psychosis is a useful animal model for studies on schizophrenia. N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]- ethylamine monohydrochloride (NE-100) had no effect on conditioned avoidance responses (CAR) in rats, whereas, the PCP-induced impairment of avoidance inhibition was attenuated by NE-100. The PCP-induced ataxia or decreased attention in rhesus monkeys was to some extent overcome by NE-100. In dogs, PCP-induced either head-weaving behavior or ataxia, effects which were blocked by NE-100. Administration of PCP led to an increase in beta-2 and a decrease in delta relative power (RP) activity in cortical background spectral electroencephalographics (ECoG) in dogs. While NE-100 in itself showed no significant change in beta-2 and delta RP, NE-100 did block the PCP-induced beta-2 increase and delta decrease. These findings indicate that NE-100 attenuates the effect of PCP in experimental animals. This drug is being considered as a therapeutic for the treatment of patients in the schizophrenia.

Animals↗

PubMed1994

Effects of VA-045, a novel apovincaminic acid derivative, on age-related impairment evidence in electroencephalograph, caudate spindle, a passive avoidance task and cerebral blood flow in rats.

1. The ability of VA-045 to improve aged-related impairment on electroencephalograph (EEG), caudate spindle, performance on a passive avoidance task and cerebral blood flow (CBF) were evaluated in rats. 2. The cortical EEG of the aged rats showed a higher incidence of spontaneous spindle burst (SSB) than seen in young rats. VA-045 decreased the incidence of SSB in aged rats. In contrast, vinpocetine increased the incidence of SSB in aged rats. 3. Electrical stimulation of the striatum in aged rats lead to a higher incidence of neocortical high voltage spindle (CS) than seen in young rats. In young rats, VA-045 had no effect on the CS, whereas an age-related increase in CS was blocked by VA-045, but was enhanced by vinpocetine. 4. There were no differences in the cortical EEG arousal response elicited by stimulation of the reticular formation of the brain stem in rats of all ages. VA-045 and vinpocetine had no effect on the cortical EEG arousal response in both young and aged rats. 5. VA-045, but not vinpocetine, attenuated the age-related decreased step through latency (STL) on a passive avoidance task. VA-045 and vinpocetine did not enhance the acquisition of learning behavior in a passive avoidance task in young rats. 6. VA-045 increased the cerebral blood flow (CBF) in both young and aged rats and the potency in aged rats was greater than that in young rats. Vinpocetine had no effect on CBF in either young or aged rats. 7. The pharmacological effects of VA-045 on age-related neuronal dysfunction are discussed.

Aging↗

PubMed1994

[In vitro antibacterial activity of fleroxacin (FLRX) against clinical isolates from bacterial enteritis].

Antibacterial activity of fleroxacin (FLRX), a new quinolone antimicrobial, against 36 strains of Shigella app., 14 strains of Salmonella spp., 11 strains of Escherichia coli, 9 strains of Vibrio spp. (including 2 strains of V. cholerae O1), 14 strains of Campylobacter jejuni/coli, 3 strains of Aeromonas spp. and 1 strain of Plesiomonas shigelloides isolated from infectious enteritis patients in this study was determined. Its activity was compared with that of ciprofloxacin (CPFX), norfloxacin (NFLX) and nalidixic acid (NA). The MIC90 values of FLRX were 0.1 microgram/ml against Shigella spp. and E. coli, 0.2 microgram/ml against Salmonella spp. and Vibrio spp., and 12.5 micrograms/ml against C. jejuni/coli MIC90 of FLRX was comparable to that of CPFX and NFLX against Vibrio spp.. Against other species, MIC90 of FLRX were 2- to 4-fold higher than those of CPFX, whereas equal to or 2-fold lower than NFLX. FLRX demonstrated excellent activity against an NA-resistant (MIC: > 100 micrograms/ml) isolate of E. coli, with MIC 0.78 microgram/ml. FLRX showed 8-fold higher activity than NA against other strains. The antibacterial activity of FLRX was compared with that of NA against stocked strains (clinical isolates from August 1989 to February 1991), consisting of 11 strains of Shigella spp., 10 strains of Salmonella spp., 8 strains of E. coli, 10 strains of V. cholerae O1, 10 strains of V. parahaemolyticus and 14 strains of C. jejuni/coli. MICs of FLRX were 0.78 and 12.5-25 micrograms/ml against Shigella spp. and C. jejuni/coli that showed resistance of NA (MIC: > or = 100 micrograms/ml), respectively. Based on the above, although the absolute MICs are low against E. coli and shigella spp., a value of 0.78 micrograms/ml for FLRX suggested that such strains should be considered to be resistant.

Campylobacter jejuni↗

PubMed1994

[Contamination of healthy livestock with verocytotoxin producing Escherichia coli (VTEC), the first isolation from goats in Japan].

As part of the investigation on the source and route of infection with Verocytotoxin producing Escherichia coli (VTEC) in human beings, isolation of VTEC was attempted using fresh feces collected from healthy livestock (cattle, swine and goat) raised in Sagamihra, Yokohama and Hiratsuka cities from October, 1991 to March, 1992. VTEC could be isolated from 1 (1.0%) of 105 swine, 2 (3.6%) of 55 cattle and 2 (15.4%) of 13 goats. VTEC was isolated for the first time from goats in Japan. The combinations of the serotype and toxin type of the isolated strains were O116:H21 (VT2) and O163:H19 (VT2) for those isolated from the cattle, OUT:H19 (VT2vp) for that from the swine and OUT:H21 (VT1) for those from the goats. Since VTEC isolated from the cattle and goats were found to produce VT of the same serotypes as human VTEC, domestic animals were considered to be involved as a source of VTEC infection in human beings.

Animals↗

PubMed1993

FH-510, a potent and selective ligand for rat brain sigma recognition sites.

FH-510 (5,8-dimethyl-4-(2-di-n-propylaminoethyl)carbazol) is a potent ligand for sigma ligand binding sites in rat brain membranes and has an IC50 value of 4.8 +/- 1.0 nM, which is comparable to that of haloperidol (2.2 +/- 0.2 nM). The high selectivity of FH-510 for sigma binding sites was evaluated by its lack of significant affinity for other binding sites, including those for dopamine D2 and phencyclidine. When administered to mice orally, FH-510 suppressed (+)-N-allylnormetazocine ((+)-SKF10,047)-induced stereotyped behavior with an ED25 value of 0.54 mg/kg, which is 14-fold more potent than that for (+)-alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol ((+)-BMY14802) (7.6 mg/kg). These results suggest that FH-510 may be a potent and selective sigma ligand.

Animals↗

PubMed1993

NE-100, a novel sigma receptor ligand: in vivo tests.

It has been suggested that sigma receptor antagonists may be useful as antipsychotic drugs. N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100) is a novel compound with high affinity for the sigma receptor (IC50 = 4.16 nM), but low affinity (IC50 > 10,000 nM) for D1, D2, 5-HT1A, 5-HT2 and phencyclidine (PCP) receptors. The head-weaving behavior induced by either (+)SKF10047 or PCP was dose-dependently antagonized by NE-100 with oral ED50 at 0.27 and 0.12 mg/kg, respectively. NE-100 did not affect dopamine agonists-induced stereotyped behavior and/or hyperactivity. NE-100 failed to induce catalepsy in rats. These findings indicate that NE-100 may have antipsychotic activity without the liability of motor side effects typical of neuroleptics.

Animals↗

PubMed1993

Effect of VA-045 on a closed head injury model in rats.

The effect of VA-045, a novel apovincaminic acid derivative, was studied in a model of closed head injury (CHI) in rats. CHI was induced by dropping a 400 g weight through a tube from 70 cm above a steel helmet placed on the vertex. Intravenous administration of VA-045 and thyrotropin-releasing hormone (TRH) reduced both the duration of loss of righting reflex and the duration of disruption of spontaneous movement caused by CHI. VA-045, but not TRH attenuated the CHI-induced decreased step through latency (STL) on a passive avoidance task. Over the same time schedule, however, VA-045 did not attenuate the scopolamine-induced decreased STL. CHI-induced reduction of the amplitude of somatosensory evoked potentials (SEP) was recovered by VA-045 but not by TRH. These findings indicate that VA-045 may be useful for treating patients with CHI-induced disturbance in consciousness.

Animals↗

PubMed1993

[Studies on hemolytic streptococcal infection: 1). Outbreak of group C hemolytic streptococcal infection in Formosan squirrels].

Between mid-October to mid-November 1992, of 500 freely-ranging Formosan and striped squirrels kept at Garden Y in the suburbs of Kanagawa Prefecture, 414 (82.8%) suddenly died one after another by bleeding from the nasal and oral cavities after developing a mild facial swelling. Isolation of microbes including viruses were carried out from the Formosan squirrels that had suddenly died. Various organs from these animals were histologically examined. 1. In bacteriological tests, beta-hemolytic streptococcal strains were isolated in a pure culture from 5 (83.3%) of 6 Formosan squirrels that had died suddenly. By serological analysis, 14 isolated strains were serotyped as group C according to the classification of Lancefield. From their biochemical characteristics, these were identified as Streptococcus equi subsp. zooepidemicus. A drug sensitivity test revealed that ABPC, PCG, SBPC, CMX and CPZ are highly sensitive against the isolates. 2. In the virological test, the viral isolation was applied for three blind passages by primary cultured kidney cells of Formosan squirrels, but no evidence of CPE was obtained. 3. At autopsy, a pathological change was detected mainly in the lungs. Histopathological examinations revealed severe hypertrophic changes of the alveolar wall in the entire pulmonary lobe. Severe congestion, hemorrhagic pneumonia, neutrophils and macrophages infiltration were observed in the hypertrophic alveolar wall. In the other cases, thrombi were observed in the branches of the pulmonary artery. Other organs demonstrated no remarkable histopathological changes. 4. Streptococcal strains were not isolated from the pharynx in all of the employees working at this garden.

Animals↗

PubMed1993

Reduced susceptibilities of Shigella sonnei strains isolated from patients with dysentery to fluoroquinolones.

Seven clinical isolates of Shigella sonnei with reduced susceptibilities to fluoroquinolones (sparfloxacin, ciprofloxacin, and ofloxacin) were obtained. The MICs of fluoroquinolones against these S. sonnei strains were 16 to 32 times higher than those obtained against typical strains that are highly susceptible to these agents. The kinetics of [14C]ofloxacin accumulation in these clinical strains were not different from those in the fully susceptible strains. However, DNA synthesis was much less inhibited by ofloxacin in the strains with reduced susceptibility. Analysis of the in vitro activity of the partially purified DNA gyrase from these isolates showed that the decreased quinolone susceptibility of the S. sonnei strains was likely due to mutation of the DNA gyrase subunit A gene.

Anti-Infective Agents↗

PubMed1993

The effect of VA-045 on disturbance in consciousness in experimental animal models.

The effect of VA-045, a novel apovincaminic acid derivative, on disturbance in consciousness was investigated in mice and rats. VA-045 and thyrotropin-releasing hormone (TRH) shortened the duration of pentobarbital-induced sleeping in rats. VA-045 and TRH improved head impact-induced disturbed behavior in mice. The duration of action of the improving effect of VA-045 was longer than that of TRH. VA-045 and TRH also ameliorated the global cerebral ischemia-induced neurological deficits. Global cerebral ischemia was produced by a 10 min occlusion of both common carotid arteries 24 hr after the permanent electrocauterization of bilateral vertebral arteries. VA-045, but not TRH, attenuated the global cerebral ischemia-induced decreased step through latency (STL) in a passive avoidance task in rats. TRH enhanced spontaneous locomotor activity in mice, whereas VA-045 had no effect on it. The pharmacological effects of VA-045 on disturbance in consciousness will be discussed.

Animals↗