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

The non-competitive NMDA receptor antagonist, MK-801 (dizocilpine), induces in rats a characteristic behavioural syndrome with ataxia, stereotypies and hyperlocomotion. At least part of this behavioural syndrome is thought to be related to interactions between glutamatergic and dopaminergic neurotransmission. Based on recent biochemical evidence that serotonin (5-HT) might also be involved in the effects of MK-801 several 5-HT receptor ligands were tested for effects on MK-801-induced behaviours. The 5-HT1A receptor ligands, ipsapirone and NAN-190, which are known to display antagonist-like properties in functional models of postsynaptic 5-HT1A receptor activity attenuated or blocked the hyperlocomotion and head weaving observed after administration of MK-801, whereas the 5-HT2 receptor antagonist, ritanserin, was ineffective in this respect. The dopamine receptor antagonist, haloperidol, and the alpha 1-adrenoceptor antagonist, prazosin, also attenuated behaviours induced by MK-801. In contrast to its effects on stereotypies induced by MK-801, ipsapirone potentiated rather than attenuated the stereotyped behaviour induced by the dopamine receptor agonist, apomorphine, indicating that antagonism of MK-801-induced stereotypies by ipsapirone may not be related to the dopaminergic system. The data indicate that, in addition to catecholaminergic systems, serotonergic neurotransmission is significantly involved in the mechanisms by which MK-801 alters behaviour in rats.
 ...
PMID:The behavioural effects of MK-801 in rats: involvement of dopaminergic, serotonergic and noradrenergic systems. 135 90

The orally active competitive N-methyl-D-aspartate (NMDA) receptor antagonists CGP 37849 (DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenoic acid) and its ethyl ester CGP 39551 were evaluated in amygdala-kindled rats, a model for complex partial and secondarily generalized seizures. Anticonvulsant and behavioral effects of these novel compounds were compared with those of the noncompetitive NMDA receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imin e] and the antiepileptic drug carbamazepine, one of the major drugs for treatment of partial and generalized seizures in humans. For comparative evaluation, the compounds were injected i.p. at the following doses: 1 to 10 mg/kg (CGP 37849 or CGP 39551), 0.05 to 0.3 mg/kg (MK-801) and 20 to 40 mg/kg (carbamazepine), respectively. In contrast to carbamazepine, CGP 37849, CGP 39551 and MK-801 exerted only weak anticonvulsant effects in fully kindled rats and did not increase the focal seizure threshold. The weak anticonvulsant effects of the NMDA receptor antagonists in kindled rats were associated with profound untoward behavioral effects. The behavioral syndrome induced by the NMDA receptor antagonists in kindled rats was characterized by marked ataxia, hyperactivity and, in case of CGP 37849 and MK-801, stereotypies, such as head weaving. The low or absent effectiveness of the novel NMDA receptor antagonists against kindled seizures suggests that these compounds will not be clinically useful antiepileptics against partial and secondarily generalized seizures. Furthermore, in view of the recent clinical findings on psychotomimetic effects of MK-801 in epileptic patients, the similarities in the excitatory effects produced by CGP 39551, CGP 37849 and MK-801 in kindled rats may indicate that competitive NMDA receptor antagonists may also produce psychotomimetic effects in humans.
 ...
PMID:Anticonvulsant and behavioral effects of two novel competitive N-methyl-D-aspartic acid receptor antagonists, CGP 37849 and CGP 39551, in the kindling model of epilepsy. Comparison with MK-801 and carbamazepine. 167 93

The novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849) was found to produce a phencyclidine (PCP)-like behavioral syndrome (ataxia, locomotion, stereotypies) in amygdala-kindled rats, whereas the amphetamine-like behavioral alterations of the syndrome (locomotion, stereotypies) were only infrequently seen in nonkindled rats. In dose-response experiments in kindled and nonkindled rats, behavioral effects were scored using a ranked intensity scale, and the behaviors and behavioural scores determined after CGP 37849 were compared with those determined after i.p. administration of the noncompetitive NMDA receptor antagonist dizocilpine maleate (MK-801). In kindled rats, 20 mg/kg of CGP 37849 produced about the same scores for hyperlocomotion and head weaving as 0.1 mg/kg of MK-801. Kindled rats exhibited higher behavioral scores than nonkindled rats, especially in the case of CGP 37849. The behavioral effects produced by CGP 37849 in kindled rats were almost indistinguishable from the PCP-like behavioral effects induced by MK-801, indicating that CGP 37849 indeed produces a PCP-like pattern of behavior in kindled rats. Hyperlocomotion and head weaving induced by CGP 37849 in kindled rats could be attenuated or totally prevented by pretreatment with ipsapirone, a partial agonist/antagonist at postsynaptic 5-hydroxytryptamine (5-HT) receptors of the 5-HT1A subtype. Furthermore, these behavioural effects were attenuated or blocked by the dopamine antagonist haloperidol and the alpha-1 adrenoceptor antagonist, prazosin. The data demonstrate that kindling induces a hypersensitivity to PCP-like behavioral effects of competitive and noncompetitive NMDA receptor antagonists, which could relate to the recent finding of increased function of NMDA receptors following kindling.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The novel competitive N-methyl-D-aspartate (NMDA) antagonist CGP 37849 preferentially induces phencyclidine-like behavioral effects in kindled rats: attenuation by manipulation of dopamine, alpha-1 and serotonin1A receptors. 167 88

Memantine (1-amino-3,5-dimethyladamantane) has previously been shown to attenuate or block chemically or electrically induced seizures in rodents at doses of 5-20 mg/kg i.p., suggesting that the drug might have potential utility in the treatment of seizures. In the present study, the effects of memantine were examined in amygdala-kindled and non-kindled rats. In fully kindled rats, i.e. a model of focal seizures with secondary generalization, memantine exerted no effects on seizure parameters at 5 mg/kg i.p., but reduced seizure severity and duration at 10 mg/kg. The threshold for induction of afterdischarges recorded from the amygdala was not altered after administration of 10 mg/kg. At 20 mg/kg, memantine induced spontaneous motor seizures in amygdala-kindled rats. No motor seizures were observed in non-kindled rats, but in both kindled and non-kindled animals memantine, 20 mg/kg, induced spikes in the electroencephalogram. Additional dose-dependent behavioural alterations observed after memantine included hyperactivity, ataxia and stereotypies, which may relate to the dopaminomimetic properties of the drug. The results demonstrate that kindled rats are more sensitive to central nervous system stimulating effects of memantine than non-kindled rats, which could relate to an impairment of inhibitory processes and/or alterations in synaptic transmission mediated by excitatory amino acids in the kindled brain.
 ...
PMID:High doses of memantine (1-amino-3,5-dimethyladamantane) induce seizures in kindled but not in non-kindled rats. 236 81

A multicentric study of 15 cases of Rett syndrome selected with the diagnostic criteria according HAG-BERG et al: female sex, normal pre and perinatal period, normal psychomotor development through the first months of life, early dementia between 1-3 years of age with autistic behaviour, loss of acquired purposeful hand skill, "washing hands" stereotypies, normal head circumference at birth with later deceleration of head growth and truncal ataxia with gait apraxia. Waking EEG showed unspecific abnormalities while sleep recording demonstrated extremely frequent multifocal spike and sharp waves mainly over the rolandic region and generalized, and also pseudo-periodic suppression of background activity. In 3 cases the EMG showed a peripheral axonal neuropathy. Only in one case we found hyperammonemia. Karyotypic studies performed in 12 cases demonstrated non specific fragile sites. CT scan was normal in almost all cases. The QD was extremely low.
 ...
PMID:[Rett's syndrome: study of 15 cases]. 245 8

We have studied an 8-year-old girl with ornithine transcarbamylase deficiency with many of the manifestations of Rett syndrome. She is profoundly mentally retarded and microcephalic after normal development in early childhood. Seizures, hyperventilation, ataxia, amimia, and "hand wringing" stereotypies are present. The distinguishing characteristic is the history of recurrent episodes of vomiting and hyperammonemic coma. This case points to the possible existence of genocopies of Rett syndrome.
 ...
PMID:A case of ornithine transcarbamylase deficiency with Rett syndrome manifestations. 308 94

Patients with Rett syndrome appear to fulfill the Rendle-Short criteria for the diagnosis of autism, but the pattern of their behavior is qualitatively different from children with autism. Until a biologic marker is identified, diagnosis is based on clinical assessment. In order to standardize this clinical assessment and to provide objective criteria for the evaluation of potential therapeutic modalities, motor and behavioral characteristics of 15 Rett patients were analyzed. The patients with Rett syndrome differed from autistic children in having ataxia, breath-holding, hyperventilation, bruxism, simplicity of stereotypies, and hand apposition. The children with autism demonstrated complex stereotypies and verbal but not motor regression. The more typical features of autism, namely, poor eye contact, lack of sustained interest, speech disturbance, and repetitive truncal rocking motions were poor discriminators between the two groups.
 ...
PMID:Rett syndrome: qualitative and quantitative differentiation from autism. 319 4

The dose-response effects of neuroleptic pretreatment on phencyclidine (PCP; 3 or 5 mg/kg)-induced locomotor activity, stereotyped behaviors and ataxia were quantified in groups of male rats using rating scales recently developed in this laboratory. Three butyrophenone neuroleptics consistently produced dose-dependent antagonism of the behavioral effects of PCP administration. Fluphenazine antagonized the behavioral effects produced by 3 mg/kg PCP but not those produced by 5 mg/kg PCP. Each of the other neuroleptics examined (chlorpromazine, thioridazine, mesoridazine, triflupromazine, cis-flupenthixol) had no consistent antagonistic effect or actually enhanced one or more of the behavioral effects of PCP. Some neuroleptics slightly reduced PCP locomotion or stereotypies at high doses, but these effects were probably a non-specific consequence of the synergistic ataxia-producing properties of these drugs. In a second set of experiments, atropine sulfate pretreatment increased PCP-induced locomotor activity and stereotyped behaviors but had no effect on ataxia; pretreatment with physostigmine produced opposite effects. Combined pretreatment with haloperidol and atropine sulfate significantly reduced only haloperidol antagonism of PCP-induced ataxia, thus suggesting that non-dopoaminergic effects of neuroleptics may interfere with their ability to antagonize PCP.
 ...
PMID:A comparison of the effects of neuroleptics on phencyclidine-induced behaviors in the rat. 611 21

The effects of naloxone, metenkephalin, and morphine were tested on phencyclidine(PCP)-induced stereotyped behaviors, ataxia, and hyperactivity in the rat. Naloxone (8 mg/kg) significantly decreased stereotypy, ataxia, and hyperactivity across all PCP doses tested (2.0, 4.0, and 6.0 mg/kg). Metenkephalin (40 micrograms/kg) and morphine (5 and 10 mg/kg) increased ataxia at the 4.0 and 6.0 mg/kg PCP doses. Stereotypy was altered by the opiates in a dose-dependent manner; enhanced by metenkephalin (40 micrograms/kg) at 2.0 mg/kg and inhibited by metenkephalin (40 micrograms/kg) and morphine (10 mg/kg) at 4.0 and 6.0 mg/kg PCP. Locomotor activity was increased by morphine (5 mg/kg) at 2 mg/kg PCP. These results suggest an involvement of central opiate receptor mechanisms in the mediation of PCP-induced behaviors in the rat.
 ...
PMID:Effects of naloxone, metenkephalin, and morphine on phencyclidine-induced behavior in the rat. 681

MK-801 (dizocilpine) is an NMDA antagonist known to cause vacuolization and necrosis in susceptible cortical neurons. The objectives of the present work were to characterize the behavioral effects produced by a single administration of MK-801 and to determine how these effects may relate to the morphological changes seen in the central nervous system. Female rats (8/ group), approximately 9 weeks of age, received one of three doses of (+)MK-801 (0.1, 0.25, and 0.5 mg/kg) subcutaneously. Behavioral evaluation, using detailed clinical observations or a functional observational battery, was conducted every 15 minutes from 15-120 minutes post dosing and on Days 2, 3 and 7. Locomotor activity was assessed on Days 1,3,7 and 14. Stereotypy and ataxia were seen in all MK-801 groups soon after dosing, and continued to be observed in the two lower dose groups out to 2 hours. By 45 minutes post dosing, most of the rats from the 0.5 mg/kg group were completely immobile and did not show recovery for several hours. At 24 hours post dosing when all animals from the 0.5 mg/kg group were mobile, stereotypy and ataxia were evident. A differential dose effect was observed on locomotor activity on Day 1. Markedly increased locomotor activity was seen in the 0.1 mg/kg group, whereas activity was decreased in the 0.5 mg/kg group. This decrease at the highest dose level continued to be seen up to 3 days post dosing. In conclusion, acute dosing with MK-801 produced a behavioral pattern that was markedly affected by the increasing severity of ataxia with increasing dose and that was similar, in many aspects, to the profile that has been seen with single dose administration of phencylidine in the rat. Comparison of the temporal pattern of behavioral change (at the 0.5 mg/kg dose level) with that of necrosis development did not suggest a direct mechanistic relationship.
 ...
PMID:Neurobehavioral profile of subcutaneously administered MK-801 in the rat. 908 14


1 2 3 4 Next >>