Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bromocriptine (CB-154) is regarded as a dopamine agonist, hence is used in the treatment of Parkinson's disease. In the paper presented a possibility of the influence of bromocriptine on central serotonin neurons has been studied. It was demonstrated that CB-154, like tryptophan, 5-hydroxytryptophan, LSD or fenfluramine in previous experiments, potentiates the flexor reflex of the spinal rat, and this effect of CB-154 is prevented by serotonin antagonists--cryproheptadine and danitracen. CB-154, like fenfluramine used as a comparative serotonergic agent, rises the body temperature in rabbits. The hyperthermic effect of CB-154 is prevented by cyproheptadine, danitracen and mianserin. Haloperidol prevents the hyperthermia caused by a lower dose of CB-154 or on fenfluramine-induced hyperthermia. The results obtained indicate that CB-154, besides a dopaminomimetic action, possesses central serotonin actions as well.
 ...
PMID:The influence of bromocriptine on serotonin neurons. 92 86

Amine accumulation is observed in the lateral hypothalamus (LH) after nigrostriatal neurons degenerate. It has been proposed that this accumulation is a source of amines which are released into the hypothalamus thereby affecting the function of adjacent aminergic receptors. To approximate this condition of continuous exposure of LH receptors to endogenous amines, dopamine (DA) was injected into the LH of rats once daily for 5 consecutive days. A control group received 4 daily injections of tartaric acid vehicle and then DA on day 5. Rats pretreated with DA showed severe impairment of open field performance and motor reflex control on day 5 when they were compared to control animals which received vehicle pretreatment. In a second study, the DA receptor antagonist haloperidol was injected into the area of amine accumulation in the LH to determine whether this might block amine release from areas of accumulation thereby to attenuate lesion-induced rotation. Haloperidol administered once daily for 4 out of 7 days, once daily for 7 days or via a continuous infusion for 7 days, all reduced d,l-amphetamine-induced turning to control levels. These results suggest that prolonged exposure of hypothalamic DA receptors alters their sensitivity to subsequent doses of DA and that amine released from areas of accumulation may be blocked by haloperidol to enhance behavioral recovery from DA depleting lesions. Moreover, these findings indicate that the hypothalamus participates in the behavioral effects induced by DA depleting lesions and highlight the importance of hypothalamic pathology in Parkinson's disease.
 ...
PMID:Sensitivity of dopamine receptors in the lateral hypothalamus is altered in 6-hydroxydopamine treated rats. 134 83

In the present study, quantitative in situ hybridization was used to analyse the effect of haloperidol treatment on D2 dopamine receptor gene expression in the rat caudate-putamen nucleus. Variations of D2 receptor mRNA level were studied and measured at the macroscopic level of densitometric analysis of X-ray film and at the microscopic level by counting of autoradiographic silver grains in striatal cells. Macroscopic analysis demonstrated that haloperidol treatment two times 1 mg/kg per day during seven, 14 and 21 days increased D2 receptor mRNA level in the caudate-putamen. Detailed microscopic analysis demonstrated a significant increase in D2 receptor mRNA in the two neuronal populations known to express the D2 receptor gene: medium-sized neurons previously identified as enkephalinergic neurons, and large-sized neurons previously identified as cholinergic neurons. The increase was more important in cholinergic neurons (+119%) than in enkephalinergic neurons (+54%). Haloperidol treatment did not modify the number of medium-sized enkephalinergic neurons expressing the D2 receptor mRNA. In contrast, it significantly increased the percentage of large-sized neurons containing D2 receptor mRNA (from 80 to 94%). These results demonstrate that haloperidol treatment acts at the gene level to modulate D2 receptor content in striatal dopaminoceptive neurons, and that the D2 receptor mRNA increase in postsynaptic neurons contributes to dopamine supersensitivity induced by neuroleptics in the rat. This suggests that dopamine acts trans-synaptically to control D2 receptor gene expression in target striatal neurons. These results suggest that modifications of D2 receptor gene expression may be part of the biological events that lead to the movement disorders induced by neuroleptic drugs or Parkinson's disease.
 ...
PMID:Striatal neurons express increased level of dopamine D2 receptor mRNA in response to haloperidol treatment: a quantitative in situ hybridization study. 175 61

Antipsychotic drugs, while ameliorating symptoms in schizophrenia, evoke extrapyramidal effects which resemble parkinsonism. We studied the potential of 1- (4,4-bis(4-fluorophenyl)butyl)-4-(4-fluorophenoxy)-1,2,3,6-tetrahydropyr idine d-tartrate to induce extrapyramidal side effects in Rhesus monkeys. This agent shares neurochemical effects of known antipsychotic agents in its ability to antagonize cerebral dopamine action by competing for (3H)-Haloperidol binding of the dopamine receptors and inhibiting limbic and striatal adenylate cyclase in rat brain. The compound was administered orally to monkeys for 18 days, starting at 2 mg/kg and increasing to 20 mg/kg. Additional groups of monkeys received the drug for 29 consecutive days at 5 and 7.5 mg/kg/day. In both studies, extrapyramidal signs were associated with neuropathological changes in the brains of treated monkeys. The findings resemble those reported in Rhesus monkeys and in drug addicts after repeated intravenous administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The findings also suggest a structure/activity relationship of tetrahydropyridine analogs with neurologic and associated neuropathologic manifestations produced in monkeys. The experimental model is useful to study the pathogenesis and possibly therapeutic approaches for Parkinson's disease.
 ...
PMID:Parkinson-like syndrome in nonhuman primates receiving a tetrahydropyridine derivative. 348 56

Haloperidol-induced (0.25-1.0 mg/kg) catalepsy in rats is characterized by rhythmic time fluctuations. Marked catalepsy was accompanied by slow regular waves at 2-4 and 5-7 min period. Natural or L-dopa-induced inhibition of the process involves the phase of irregular and frequent fluctuations. The study of time fluctuations of the muscular tone are believed important for predicting the development of drug-induced Parkinson's disease.
 ...
PMID:[Minute rhythms of haloperidol catalepsy in rats]. 394 22

Cats were trained to walk on a specially designed treadmill: the cats were able to collect food pellets by switching motor patterns with or without the help of exteroceptive stimuli inherent to the treadmill. To study the involvement of the caudate nucleus in switching motor patterns cats received intracaudate bilateral injections of haloperidol. In addition, in a final series of experiments, EMG recordings of two antagonistic muscles, together with recordings of characteristic changes in the length of one muscle, were made before and after the haloperidol treatment. Haloperidol treatment resulted in a decreased number of motor patterns which were not directed by exteroceptive stimuli (non-exteroceptively directed motor patterns). This haloperidol-induced effect was dose-dependently counteracted by the additional intracaudate injections of apomorphine which per se remained ineffective. Haloperidol neither altered the number of food collecting attempts nor reduced the number of exteroceptively directed motor patterns. Furthermore, haloperidol did not affect the capacity to switch to proprioceptively directed motor patterns. Finally, haloperidol did not produce abnormalities in EMG and length signals recorded from hindlimb muscles. It is concluded that haloperidol selectively reduced the animal's capacity to 'programme non-stimulus directed motor behaviour'. The data are discussed in view of their significance for therapy of patients with basal ganglia disorders, such as patients suffering from Parkinson's disease.
 ...
PMID:Caudate nucleus and programming behaviour in cats: role of dopamine in switching motor patterns. 609 85

Circadian rhythms of prolactin have been evaluated in thirteen untreated parkinsonian patients before and after 15 days of treatment with L-Dopa + carbidopa. The 24th secretory pattern was not significatively different from that observed in controls. The L-Dopa + carbidopa therapy does not change the basal circadian prolactin (PRL) rhythm. These results suggest that the tubero-infundibular dopaminergic system (TIDA) and the PRL secretion are conserved in untreated parkinsonian patients (PP). During chronic L-Dopa + carbidopa therapy, the basal PRL levels, evaluated in 21 PP, showed a correlation with the severity of clinical features. The effects of single doses of apomorphine, bromocriptine, lisuride and haloperidol, were studied on serum levels of PRL in 21 PP divided in two groups of "responders" and "non-responders". Haloperidol induced an enhancement of serum PRL; the dopaminergic drugs, apomorphine, bromocriptine and lisuride inhibited basal PRL secretion. It seems that the TIDA system, in Parkinson disease is not significatively altered, even though presenting a remarkable slower response in "non-responders" to L-Dopa therapy. We also evaluated the effect of L-Dopa, L-Dopa + carbidopa, bromocriptine, lisuride, nomifensine and deprenyl on growth hormone secretion in six PP. The endocrine effects of dopaminergic drugs show a mild rise in comparison with controls suggesting an important alteration in the dopamine (DA) control of growth hormone (GH).
 ...
PMID:Prolactin response as an index of dopaminergic receptor function in Parkinson's disease. Correlation with clinical findings and therapeutic response. 726 25

Behavioral effects of terguride, a partial dopamine D2 agonist, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys were compared with those of the dopamine agonist apomorphine and the dopamine antagonist haloperidol. Terguride alone ameliorated the parkinsonism without inducing any sign of excitability, irritability, or aggressiveness (hyperactivity). Apomorphine alone also ameliorated the parkinsonism but induced marked hyperactivity. Haloperidol alone caused worsening of the parkinsonism, inducing transient eyelid closure. In combination with apomorphine, terguride suppressed the hyperactivity induced by apomorphine without reducing its antiparkinsonian effects. Pretreatment with haloperidol suppressed both the antiparkinsonian effects and the hyperactivity induced by apomorphine. Terguride thus exhibits both antiparkinsonian and antihyperactivity effects in a monkey model of Parkinson's disease, suggesting that terguride might be beneficial for treating motor dysfunction and dopaminergic psychosis in advanced Parkinson's disease.
 ...
PMID:Effects of terguride, a partial D2 agonist, on MPTP-lesioned parkinsonian cynomolgus monkeys. 809 31

Neuroleptic medications are prescribed to millions of patients, but their use is limited by potentially irreversible extrapyramidal side effects. Haloperidol shows striking structural similarities to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which produces parkinsonism apparently through inhibition of NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial electron transport chain. We now report that haloperidol, chlorpromazine, and thiothixene inhibit complex I in vitro in rat brain mitochondria. Clozapine, an atypical antipsychotic reported to have little or no extrapyramidal toxicity, also inhibits complex I, but at a significantly higher concentration. Neuroleptic treated patients have significant depression of platelet complex I activity similar to that seen in idiopathic Parkinson's disease. Complex I inhibition may be associated with the extrapyramidal side effects of these drugs.
 ...
PMID:Neuroleptic medications inhibit complex I of the electron transport chain. 790 2

A new therapeutic strategy for the treatment of Parkinson's disease (PD) is based on providing trophic support for degenerating dopaminergic (DA) neurons. It can be accomplished by administration of neurotrophic factors, or inducing astrocytes to differentiate and produce such factors. Antineoplaston A5 (A5), which is a naturally-occurring cytodifferentiating agent, may induce astrocytes to undergo normal differetiation, produce neurotrophic factors and alleviate the symptoms of PD. This paper describes studies on the influence of A5 on subtypes of central DA receptors by measuring the potency of haloperidol catalepsy in rats. A5, D1 agonist, and D1 D2 antagonists were given i.p. and D2 agonist s.c. for three consecutive days. Haloperidol catalepsy was measured by the method of Costall and Nylor. The degree of catalepsy was assessed every 30 min for 24 h and statistically evaluated using the Student's t-test. The results confirmed that A5 significantly attenuated catalepsy and stimulates dopamine D2 receptors. It reverses catalepsy induced by haloperidol and D2 antagonists, but increases cataleptogenic activity if given in combination with the D2 agonist. This leads to the conclusion that A5 as a naturally-occurring agent neutralizes both hyper- and hypoactivity of central dopaminergic structures. Besides possible use as an antiparkinsonism agent, A5 may find application in the treatment of other disturbances of dopaminergic transmission.
 ...
PMID:The influence of antineoplaston A5 on particular subtypes of central dopaminergic receptors. 852 28


1 2 3 4 Next >>