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

From the data discussed in this review it appears that GABA receptor agonists exhibit a variety of actions in the central nervous system, some of which are therapeutically useful (Table V). GABA receptor agonists, by changing the firing rate of the corresponding neurons accelerate noradrenaline turnover without changes in postsynaptic receptor density and diminish serotonin liberation with an up-regulation of 5HT2 receptors. These effects differ from those of tricyclic antidepressants which primarily block monoamine re-uptake and cause down-regulation of beta-adrenergic and 5HT2 receptors. The GABA receptor agonist progabide has been shown to exert an antidepressant action which is indistinguishable from that of imipramine in patients with major affective disorders. The fact that: (a) GABA receptor agonists and tricyclic antidepressants affect noradrenergic and serotonergic transmission differently; and (b) tricyclic antidepressants alter GABA-related parameters challenges the classical monoamine hypothesis of depression and suggests that GABA-mediated mechanisms play a role in mood disorders. Decreases in cellular excitability produced by GABAergic stimulation leads to control of seizures in practically all animal models of epilepsy. GABA receptor agonists have a wide spectrum as they antagonize not only seizures which are dependent on decreased GABA synaptic activity but also convulsant states which are apparently independent of alterations in GABA-mediated events. These results in animals are confirmed in a wide range of human epileptic syndromes. GABA receptor agonists decrease dopamine turnover in the basal ganglia and antagonize neuroleptic-induced increase in dopamine release. On repeated treatment, progabide prevents or reverses the neuroleptic-induced up-regulation of dopamine receptors in the rat striatum and antagonizes the concomitant supersensitivity to dopaminomimetics. Behaviorally, GABA receptor agonists diminish the stereotypies induced by apomorphine or L-DOPA suggesting that GABAergic stimulation results also in an antidopaminergic action which is exerted beyond the dopamine synapse. These effects of GABA receptor agonists may represent the basis of the antidyskinetic action of these compounds which, however, remains to be fully confirmed. GABA receptor agonists reduce striatal acetylcholine turnover, an effect which occurs at doses much lower than those which affect dopamine neurons. Since hyperactivity of cholinergic neurons plays a determinant role in the pathogenesis of some parkinsonian symptoms, it is conceivable that GABAergic stimulation is effective in ameliorating Parkinson's disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:GABA receptor agonists: pharmacological spectrum and therapeutic actions. 298 90

The images of cranial computed tomographies on 7.921 patients aging between 50 and 98 years were analyzed retrospectively concerning the occurrence of WMLA. 3.344 patients were suffering from psychogeriatric disorders (organic brain syndrome, dementia, depressive or delusional psychoses). Neurological diagnoses (stroke, TIA, Parkinson's disease, Huntington's disease, space occupying lesions, seizures, cerebral trauma, vertigo, chronic headache) occurred in 4.577 patients. WMLA was established in 761 cases. The combination of WMLA with cerebral atrophies, with single or multiple infarcts and with both infarcts and atrophy will be demonstrated within 4 groups: 1. organic brain syndrome and dementia, 2. depression and delusional states, 3. stroke and TIA, 4. other neurological diagnoses. In group one the combination of WMLA with atrophy and infarcts is the most common finding in CT. In group two WMLA without atrophies and infarcts are the main tissue changes in CT. Group three is marked mainly by the occurrence of recent infarcts together with WMLA. In group four again WMLA only, in some cases together with multiple infarcts, do occur mainly. Compared to the cases without WMLA in each group WMLA is seen in cases with organic brain syndromes and dementias three to five times more than in the other diagnostic groups. WMLA in computed tomography seems to be a common finding in patients and healthy individuals of old age. Therefore the diagnostic and differential diagnostic significance for brain diseases in old age is limited. Nevertheless in the field of psychogeriatric disorders it may be possess a certain value to understand the nature of such diseases. This value will be discussed and demonstrated considering the pathogenesis of WMLA on the basis of neuropathological results.
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PMID:[Periventricular attenuation of the density of cerebral hemisphere white matter in computerized tomography of neuropsychiatric patients in the 2d half of life. Diagnostic significance and pathogenesis]. 322 Apr 19

There is a paucity of trained neurologists in developing countries. We designed a questionnaire to rapidly screen a community of 851 people (Parsis living in a colony in Bombay, India) for possible neurologic diseases. This questionnaire was pretested and found to have a sensitivity of 100 percent for detecting epilepsy, febrile seizures (only in children), completed stroke, peripheral neuropathy, movement disorders, cerebral palsy, mental retardation, and severe dementia. The screening questionnaire was administered by trained lay health workers. One hundred and sixty-three people were identified by this questionnaire as possibly having neurologic disease. Neurologists later examined these 163 people and found that 80 of them actually suffered from at least one of the neurologic diseases of interest (positive predictive value = 48 percent). The most common neurologic disorders were peripheral neuropathy (32 cases), essential tremor (13 cases), stroke (12 cases), Parkinson's disease (six cases), and epilepsy (four cases).
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PMID:Pilot survey of the prevalence of neurologic disorders in the Parsi community of Bombay. 333 Jun 62

The prevalence of functional disability in persons with cerebral palsy, epilepsy, stroke, Parkinson's disease, and severe dementia was assessed in a survey of every household in Copiah County, Mississippi, and all chronic-care institutions serving that county. Of the 23,842 residents evaluated, 246 had moderate to severe functional impairment accompanied by one or more of the aforementioned neurological disorders; 108 were not fully ambulatory; 59 required constant supervision because of cognitive difficulties; 54 were having at least one afebrile seizure monthly; and 25 experienced some combination of these impairments. Overall, prevalence ratios for these impairments increased markedly with age.
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PMID:Functional disability associated with major neurologic disorders. Findings from the Copiah County Study. 375 60

The article reviews the problems involved in perioperative care of patients suffering from myasthenia gravis, multiple sclerosis, Parkinson's disease as well as diseases associated with seizures or convulsions. The pros and cons of the various methods of anaesthesia are described. The problems associated with the anaesthesiological care of psychiatric patients are explained particularly regarding interactions between neuroleptics and narcosis. General rules preference of a specific method of anaesthesia in neurological and psychiatric patients do not exist.
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PMID:[Anesthesia in patients with neurologic and psychiatric diseases]. 689 Jul 78

This paper reviews the special indications for ECT. Included among these are delusional depression, affective illness which occurs in the geriatric population, depressions which are not responsive to pharmacologic intervention; depressed manic or schizophrenic patients who do not tolerate medication side effects; and drug-refractory Parkinson's disease. Technological advantages which have increased the safety of the procedure while reducing the side effects include: brief pulse electrical stimulation of the seizure, nondominant unilateral placement of electrodes, and simultaneous monitoring of EEG and EKG during the procedures. Finally, the five steps designed to address psychological issues as they relate to ECT are outlined and ECT is placed into the perspective of an overall therapeutic strategy in treating the patients.
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PMID:Electroconvulsive therapy in the eighties: technique and technologies. 714 86

L-Deprenyl (selegiline) is an irreversible inhibitor of monoamine oxidase type B, but also exerts several effects on dopamine and noradrenaline systems independent of monoamine oxidase type B inhibition. Thanks to these properties, L-deprenyl has gained wide acceptance in the therapy of Parkinson's disease by using L-deprenyl both with levodopa and alone. Furthermore, L-deprenyl improves the performance of patients with Alzheimer's disease. Epilepsy, particularly temporal lobe epilepsy with complex-partial seizures, is often associated with disturbances of cognitive function and behavior, and it has been suggested that a drug combining cognition-enhancing and antiepileptic activity would be of benefit in the treatment of epileptic patients. This prompted us to study if L-deprenyl exerts anticonvulsant efficacy in amygdala-kindled rats, i.e., a useful model of complex-partial seizures in humans. In addition to anticonvulsant activity, i.e., effects on already developed seizures, we determined whether L-deprenyl exhibits antiepileptogenic properties, i.e., suppressive effects on development of kindling. In all experiments, behavioral alterations of the rats in response to L-deprenyl were monitored closely. In order to assess the role of active metabolites in the anticonvulsant and behavioral effects of L-deprenyl in the kindling model, the D-enantiomer of deprenyl, which is metabolized to more potent compounds (D-amphetamine and D-methamphetamine) than the L-enantiomer, was used for comparison. In fully kindled rats, L-deprenyl potently increased the threshold for focal afterdischarges. The most marked increase in afterdischarge threshold (up to 250% above control) was seen after a dose of 10 mg/kg, whereas the D-enantiomer was ineffective at this dosage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anticonvulsant and antiepileptogenic effect of L-deprenyl (selegiline) in the kindling model of epilepsy. 761 14

N-methyl-D-aspartate receptors, found throughout the mammalian brain, are a component of the major excitatory transmitter system. Strong evidence exists that N-methyl-D-aspartate receptors, by promoting excessive entry of Ca2+ into neurons, play a role in neuronal damage that follows head injury, strokes, and epileptic seizures, and is associated with degenerative diseases such as Alzheimer's disease. Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. We have investigated whether N-methyl-D-aspartate receptors exist in peripheral neurons, and, if so, whether their activation may result in tissue injury. We report that N-methyl-D-aspartate receptors exist in the lung, that their activation triggers acute injury, and that, as in toxicity to central neurons, this injury is associated with stimulation of nitric oxide synthesis, and can be attenuated by inhibition of this synthesis. Finally, vasoactive intestinal peptide, which protects the lung and heart against oxidant injury and promotes neuronal survival and differentiation also prevented N-methyl-D-aspartate lung injury, apparently by inhibiting a key neurotoxic action of nitric oxide, but not its production. The findings suggest that N-methyl-D-aspartate receptors exist in the peripheral nervous system and that activation of these receptors, resulting in damage to peripheral neurons, may be a novel mechanism of lung and other organ injury.
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PMID:N-methyl-D-aspartate receptors outside the central nervous system: activation causes acute lung injury that is mediated by nitric oxide synthesis and prevented by vasoactive intestinal peptide. 761 71

The effects of co-administration of quinpirole with benzazepine D1 dopamine (DA) agonists possessing full/supramaximal (SKF 80723 and SKF 82958), partial (SKF 38393 and SKF 75670) and no efficacies (SKF 83959) in stimulating adenylate cyclase (AC) were investigated in rodent and primate models of Parkinson's disease (PD). In rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle, co-administration of SKF 38393 (7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine), SKF 75670 (3-CH3 analogue), SKF 80723 (6-Br analogue), SKF 83959 (6-Cl, 3-CH3, 3'-CH3 analogue) and SKF 82958 (6-Cl, 3-C3H5 analogue) strongly potentiated the contralateral circling induced by quinpirole. In MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) treated common marmosets, administration of quinpirole alone increased locomotor activity and reversed motor deficits. Grooming and oral activity were unaltered. Co-administration of SKF 38393 and SKF 75670 inhibited the quinpirole-induced changes in locomotor activity and motor disability. The combined treatment of SKF 80723 or SKF 82958 with quinpirole had no overall effect on locomotor activity or motor disability. In contrast, SKF 83959 extended the duration of the quinpirole-induced increase in locomotor activity with corresponding decreases in motor disability. Co-administration of high doses of SKF 82958 and more especially SKF 83959 and SKF 80723, with quinpirole induced hyperexcitability and seizures. Oral activity and grooming were unaltered following the co-administration of benzazepine derivatives with quinpirole. The ability of some benzazepine D1 DA agonists to prolong the antiparkinsonian effects of quinpirole in the MPTP-treated marmoset may indicate a role for certain D1 DA agonists in the clinical treatment of PD. In general, the behavioural responses to the combined administration of benzazepines with quinpirole in the 6-OHDA lesioned rat and more especially the MPTP-treated marmoset failed to correlate with their ability to stimulate AC. These observations further implicate a behavioural role for D1 DA receptors not linked to AC.
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PMID:The differential behavioural effects of benzazepine D1 dopamine agonists with varying efficacies, co-administered with quinpirole in primate and rodent models of Parkinson's disease. 777 Jun 4

Dyskinesias commonly appear during L-dihydroxyphenylalanine (L-DOPA) therapy of advanced Parkinson's disease (PD) and can occur in both dose-related and dose-independent patterns. Clozapine exerts a dose-related suppression of L-DOPA-induced dyskinesias by shifting the i.v. L-DOPA dose-response curve for production of dyskinesias without altering relief of parkinsonism. We report our outpatient experience with 13 patients on daily clozapine therapy (maximum dose 400 mg/day), followed for 3-21 months (median 10). Beneficial effects of clozapine, determined from twice-weekly diaries, included increased "on time" and decreased "off time" and time "on with dyskinesia." Improvements were statistically apparent by 75 mg/day and remained so through 200 mg/day. Sedation was a common problem, reflected by increased time "asleep" which was significant by 50 mg/day. Sedation was dose limiting in most patients. Orthostatic hypotension and sialorrhea were variably present. No patients had seizures, bone marrow toxicity, or detectable loss of efficacy of clozapine with chronic use. We conclude that clozapine is an effective agent for suppression of dyskinesias in PD with an effective daily dose for most patients of 100-200 mg/day.
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PMID:Suppression of dyskinesias in advanced Parkinson's disease: moderate daily clozapine doses provide long-term dyskinesia reduction. 796 7


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