Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of Chlorpromazine (CPZ), Haloperidol (HLP), Pentobarbital (PTB), and Diazepam (DZP) upon thresholds of the hypothalamically elicited rage response, i.e., directed attack and treat responses, were studied in chronic cats. All these drugs elevated the directed attack thresholds. CPZ and HLP elevated also the threat response thresholds and produced ataxia, but DZP did not show these effects. From these results, it is suggested that CPA and HLP suppressed the amygdalo-ventromedial hypothalamic nuclear and cerebellar functions and DZP suppressed the afferent pathway of the direct attack. PTB showed intermediate effects between the above two groups.
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PMID:Effects of psychotropic drugs upon the hypothalamic rage response in cats. 102 47

The effect of excitatory amino acid receptor antagonists, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5, 10-imine hydrogen maleate ((+)-MK-801), (+/-)-3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (CPP), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and (+/-)-2-amino-4-phosphonobutanoic acid (AP-4), on penile erection and yawning induced by subcutaneous apomorphine (80 micrograms/kg), intracerebroventricular (i.c.v.) oxytocin (30 ng) and adrenocorticotropin (ACTH)-(1-24) (10 micrograms) was studied in male rats. Intraperitoneal (0.1-0.4 mg/kg) and i.c.v. (10-50 micrograms) (+)-MK-801 prevented dose dependently the penile erection and yawning induced by the three drugs. The (+)-MK-801 effect coincided with the appearance of head weaving, body rolling, hyperlocomotion and ataxia. Haloperidol (0.5 mg/kg i.p.) antagonized the prevention by (+)-MK-801 of oxytocin responses. Penile erection but not yawning was also prevented by high, but not low doses of CPP and CNQX, which impaired motor performance, AP-4 was ineffective at all doses tested. The above compounds were ineffective when injected into the paraventricular nucleus of the hypothalamus, the brain area where apomorphine and oxytocin act to induce penile erection and yawning. The results suggest that excitatory amino acid transmission is not involved in the expression of penile erection and yawning induced by the above compounds.
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PMID:Effect of excitatory amino acid receptor antagonists on apomorphine-, oxytocin- and ACTH-induced penile erection and yawning in male rats. 135 47

The effects of BMY-14802 (5, 10, or 20 mg/kg), a sigma-receptor ligand showing preclinical evidence of antipsychotic efficacy, were tested on single-unit activity in the neostriatum of freely moving rats with or without pretreatment with 1.0 mg/kg D-amphetamine. Relative to resting baseline, amphetamine activated the large majority of neurons that changed firing rate in close temporal association with movement. All doses of BMY-14802 reversed this neuronal response, but the effect was most pronounced at 20 mg/kg. This dose, however, was equally likely to reverse or to induce a haloperidol-like potentiation of those neurons inhibited by amphetamine. In contrast, 10 mg/kg BMY-14802 consistently reversed amphetamine-induced neuronal inhibitions. All doses of BMY-14802 attenuated the locomotor effects of amphetamine, but only the higher doses also blocked other aspects of the amphetamine behavioral response. By itself, BMY-14802 dose dependently inhibited motor-related neurons, but elicited less behavioral activation than amphetamine. BMY-14802 (20 mg/kg) also induced hindlimb ataxia and occasional backwards locomotion. Haloperidol (1.0 mg/kg) reliably suppressed both behavior and neuronal activity when injected 30 min after BMY-14802, whether or not amphetamine pretreatment was given. Thus, BMY-14802 shares with other neuroleptics the capacity to reverse amphetamine-induced excitations of neostriatal motor-related neurons, whereas other effects of BMY-14802 reveal some haloperidol-like actions at 20 mg/kg that do not occur at lower doses.
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PMID:BMY-14802, a sigma ligand and potential antipsychotic drug, reverses amphetamine-induced changes in neostriatal single-unit activity in freely moving rats. 136 Dec 49

We investigated 13 patients with Huntington's disease and assessed gait by filming and by gait analyzer before and after increasing haloperidol dosage, until chorea was suppressed or side effects intervened. The severity of chorea and ataxia was scored blindly from videotapes. Gaits were abnormal in 12 of 13 patients and 5 of 6 patients who had symptoms for less than 5 years. Clinical characteristics included wide-based station, lateral swaying, spontaneous knee flexion, variable cadence, and parkinsonian features. Biomechanical analysis illustrated that gait characteristics varied in each walk, with a mean decrease in velocity, stride length, and cadence. Haloperidol treatment decreased chorea but did not affect gait patterns. Ataxia occurs early in the disease, has a distinct but variable pattern, is unrelated to chorea, and is not improved by haloperidol.
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PMID:The gait abnormality of Huntington's disease. 316 9

Low doses of the uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) induce locomotor stimulation in mice, whereas higher doses are associated with ataxia, stereotyped behaviors and catalepsy. We investigated the role of dopamine receptors and presynaptic dopamine neurons in the locomotor effects of dizocilpine. For comparison, we studied several other drugs that induce locomotor stimulation in mice. Pretreatment of male mice with haloperidol (0.1 mg/kg, i.p.) completely prevented the stimulation of normally coordinated locomotion induced by a non-intoxicating dose of dizocilpine (0.1 mg/kg, i.p.); haloperidol also attenuated the locomotor stimulation produced by phencyclidine (PCP, 1 and 2 mg/kg, i.p.), d-amphetamine (2 and 5 mg/kg, i.p.) and diazepam (0.5 mg/kg, i.p.). Haloperidol (doses up to 2.5 mg/kg) did not attenuate the ataxia and decreased locomotion induced by higher doses of dizocilpine (1 and 2 mg/kg). The active cis isomer of flupenthixol (0.5 mg/kg, i.p.), an antagonist of both D1 and D2 dopamine receptors, also diminished the stimulant actions of all of the test drugs, whereas its inactive trans form did not. The selective D1 antagonist R(+/-)-SCH 23390 (0.1 mg/kg) and the selective D2 antagonist raclopride (1 mg/kg) had little effect on the stimulatory effect of dizocilpine, although they did reduce the stimulation produced by PCP, d-amphetamine and diazepam. However, pretreatment with a combination of R(+/-)SCH 23390 and raclopride completely prevented dizocilpine-induced locomotor stimulation. Pretreatment with alpha-methyl-p-tyrosine (AMPT, 50 and 250 mg/kg), an inhibitor of tyrosine hydroxylase, or with 6-hydroxydopamine (6-OH-DA, 50 micrograms, i.c.v.), a neurotoxin that destroys brain dopaminergic and noradrenergic neurons, did not attenuate the locomotor stimulation induced by dizocilpine, although these treatments did reduce the stimulant effects of d-amphetamine. In AMPT or 6-OH-DA pretreated mice, haloperidol (0.125 mg/kg) prevented the stimulatory effect of dizocilpine. These results support a role for dopamine receptors in the stimulation of normally coordinated locomotion by dizocilpine. However, the locomotor stimulant effect of dizocilpine, unlike that of d-amphetamine, can be expressed in the presence of D1 or D2 dopamine receptor blockade and does not appear to be dependent on intact presynaptic mechanisms.
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PMID:Effects of D1 and D2 dopamine receptor antagonists and catecholamine depleting agents on the locomotor stimulation induced by dizocilpine in mice. 856 5

Phencyclidine (PCP) can induce a model psychosis in humans that mimics the positive and negative symptoms of schizophrenia. The purpose of the present study was to determine whether PCP can induce similar behavioural effects in rats and whether these effects can be alleviated by neuroleptic drug treatment. Rats were tested in the social interaction test, and their behaviour was quantified by an automated video-tracking system and manual scorings of stereotyped behaviour and ataxia. The behavioural effects of different dose- and administration regimes of PCP were initially determined, and it was found that PCP dose-dependently induced stereotyped behaviour and social isolation in the rats. Comparison to clinical studies suggests that these behaviours correspond to certain aspects of the positive and negative symptoms, respectively, of a PCP psychosis in humans. Subsequently, the effects of 3 or 21 days of administration of the antipsychotic drugs haloperidol or clozapine on the behaviour of either vehicle- or PCP-treated rats were determined. Haloperidol did not produce a selective antagonism of PCP, whereas chronic clozapine selectively inhibited the PCP-induced stereotyped behaviour and social isolation. These effects of haloperidol and clozapine suggest that this animal model can determine the effects of neuroleptic drugs on positive and negative symptoms, onset of action, and side-effect profile, including effects on the motor system. Together these data suggest that this may be a possible animal model of the positive and negative symptoms of schizophrenia.
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PMID:Phencyclidine-induced stereotyped behaviour and social isolation in rats: a possible animal model of schizophrenia. 1122 90

Acute agitation occurs in a variety of medical and psychiatric conditions, and when severe can result in behavioural dyscontrol. Rapid tranquillisation is the assertive use of medication to calm severely agitated patients quickly, decrease dangerous behaviour and allow treatment of the underlying condition. Intramuscular injections of typical antipsychotics and benzodiazepines, given alone or in combination, have been the treatment of choice over the past few decades. Haloperidol and lorazepam are the most widely used agents for acute agitation, are effective in a wide diagnostic arena and can be used in medically compromised patients. Haloperidol can cause significant extrapyramidal symptoms, and has rarely been associated with cardiac arrhythmia and sudden death. Lorazepam can cause ataxia, sedation and has additive effects with other CNS depressant drugs.Recently, two fast-acting preparations of atypical antipsychotics, intramuscular ziprasidone and intramuscular olanzapine, have been developed for treatment of acute agitation. Intramuscular ziprasidone has shown significant calming effects emerging 30 minutes after administration for acutely agitated patients with schizophrenia and other nonspecific psychotic conditions. Intramuscular ziprasidone is well tolerated and has gained widespread use in psychiatric emergency services since its introduction in 2002. In comparison with other atypical antipsychotics, ziprasidone has a relatively greater propensity to increase the corrected QT (QTc) interval and, therefore, should not be used in patients with known QTc interval-associated conditions. Intramuscular olanzapine has shown faster onset of action, greater efficacy and fewer adverse effects than haloperidol or lorazepam in the treatment of acute agitation associated with schizophrenia, schizoaffective disorder, bipolar mania and dementia. Intramuscular olanzapine has been shown to have distinct calming versus nonspecific sedative effects. The recent reports of adverse events (including eight fatalities) associated with intramuscular olanzapine underscores the need to follow strict prescribing guidelines and avoid simultaneous use with other CNS depressants. Both intramuscular ziprasidone and intramuscular olanzapine have shown ease of transition to same-agent oral therapy once the episode of acute agitation has diminished. No randomised, controlled studies have examined either agent in patients with severe agitation, drug-induced states or significant medical comorbidity. Current clinical experience and one naturalistic study with intramuscular ziprasidone suggest that it is efficacious and can be safely used in such populations. These intramuscular atypical antipsychotics may represent a historical advance in the treatment of acute agitation.
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PMID:Pharmacological management of acute agitation. 1591 48

Intramuscular injection of haloperidol or epinephrine in a minimum effective dose produces the maximum antipsychotic effect in rat model of schizophrenia, i.e. completely removes stereotypy, hyperlocomotion, and ataxia induced by MK-801. Haloperidol in the specified dose induces catalepsy, while epinephrine exhibits no cataleptogenic effect. Combined intramuscular injection of haloperidol and epinephrine in the threshold doses, ineffective in monotherapy, causes the maximum antipsychotic effect, but not catalepsy. Preliminary anesthesia of the gastric mucosa with 1% lidocaine and blockade of intramural ganglia in the gastric mucosa with hexamethonium completely abolished the potentiated antipsychotic effects produced by combined treatment with haloperidol and epinephrine. Hence, potentiation of the antipsychotic effect of haloperidol with epinephrine is related to stimulation of afferents in the gastric mucosa.
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PMID:Epinephrine potentiates antipsychotic, but not cataleptogenic effect of haloperidol in rats. 1823 84

Compounds with anti-glutamatergic properties currently in clinical use for various indications (eg Alzheimer's disease, epilepsy, psychosis, mood disorders) have potential utility as novel treatments for alcoholism. Enhanced sensitivity to certain acute intoxicating effects (ataxia, sedative) of alcohol may be one mechanism by which anti-glutamatergic drugs modulate alcohol use. We examined the effects of six compounds (memantine, dextromethorphan, haloperidol, lamotrigine, oxcarbazepine, and topiramate) on sensitivity to acute intoxicating effects of ethanol (ataxia, hypothermia, sedation/hypnosis) in C57BL/6J mice. Analysis of topiramate was extended to determine the influence of genetic background (by comparison of the 129S1, BALB/cJ, C57BL/6J, DBA/2J inbred strains) and prior stress history (by chronic exposure of C57BL/6J to swim stress) on topiramate's effects on ethanol-induced sedation/hypnosis. Results showed that one N-methyl-D-aspartate receptor (NMDAR) antagonist, memantine, but not another, dextromethorphan, potentiated the ataxic but not hypothermic or sedative/hypnotic effects of ethanol. Haloperidol increased ethanol-induced ataxia and sedation/hypnosis to a similar extent as the prototypical NMDAR antagonist MK-801. Of the anticonvulsants tested, lamotrigine accentuated ethanol-induced sedation/hypnosis, whereas oxcarbazepine was without effect. Topiramate was without effect per se under baseline conditions in C57BL/6J, but had a synergistic effect with MK-801 on ethanol-induced sedation/hypnosis. Comparing inbred strains, topiramate was found to significantly potentiate ethanol's sedative/hypnotic effects in BALB/cJ, but not 129S1, C57BL/6J, or DBA/2J strains. Topiramate also increased ethanol-induced sedation/hypnosis in C57BL/6J after exposure to chronic stress exposure. Current data demonstrate that with the exception of MK-801 and haloperidol, the compounds tested had either no significant or assay-selective effects on sensitivity to acute ethanol under baseline conditions in C57BL/6J. However, significant effects of topiramate were revealed as a function of co-treatment with an NMDAR blocker, genetic background, or prior stress history. These findings raise the possibility that topiramate and possibly other anti-glutamatergic drugs could promote the acute intoxicating effects of ethanol in specific subpopulations defined by genetics or life history.
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PMID:Effects of topiramate and other anti-glutamatergic drugs on the acute intoxicating actions of ethanol in mice: modulation by genetic strain and stress. 1884 65

Schizophrenia is a complex constellation of positive, negative and cognitive symptoms. Acute administration of the non-competitive antagonist of the N-methyl-d-aspartate receptor (NMDAR) dizocilpine (MK801) in rats is one of few preclinical animal models of this disorder that has both face and/or construct validity for these multiple at-risk behavioral domains and predictive power for the efficacy of therapeutic drugs in treating them. This study asked whether and to what extent the rat NMDAR hypofunction model also embodies the sex differences that distinguish the symptoms of schizophrenia and their treatment. Thus, we compared the effects of acute MK801, with and without pretreatment with haloperidol or clozapine, on seven discrete spontaneous open-field activities in adult male and female rats. These analyses revealed that MK801 was more effective in stimulating ataxia and locomotion and inhibiting stationary behavior in females while more potently stimulating stereotypy and thigmotaxis and inhibiting rearing and grooming in males. Haloperidol and clozapine pretreatments had markedly different efficacies in terms of behaviors but strong similarities in their effectiveness in male and female subjects. These results bear intriguing relationships with the complex male/female differences that characterize the symptoms of schizophrenia and suggest possible applications for acute NMDAR hypofunction as a preclinical model for investigating the neurobiology that underlies them.
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PMID:Acute N-methyl-D-aspartate receptor hypofunction induced by MK801 evokes sex-specific changes in behaviors observed in open-field testing in adult male and proestrus female rats. 2308 19


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