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)

Spinal anesthesia was given to a patient with right femur fracture and Parkinson's disease (PD). Although sufficient analgesia was obtained up to L1 level after spinal anesthesia, the muscular rigidity remained. Furthermore, tremor of the upper extremities continued. After administering dantrolene sodium (DT) intravenously, these untoward features were abolished. These findings suggest that DT abolishes rigidity and tremor in PD, and is useful for the management of anesthesia for a patient with PD.
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PMID:[Rigidity abolished by intravenous dantrolene in a patient with Parkinson's disease under spinal anesthesia]. 156 May 88

Sensory symptoms related to pain perception have been reported to occur in 30-50% of parkinsonian patients. Two patients with Parkinson's disease are reported, in whom painful sensory phenomena preceded or accompanied the disease process. In both patients the sensory phenomena were unresponsive to therapy with oral narcotics, anti-inflammatory drugs or administration of levodopa/carbidopa. Benzhexol (4-6 mg/day) produced dramatic amelioration of symptoms, indicating a role for the cholinergic system in the pathophysiology of abnormal sensory symptoms in Parkinson's disease and possibly in human analgesia in general.
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PMID:Anticholinergic-induced analgesia: possible role for the cholinergic system in abnormal sensory symptoms in Parkinson's disease. 243 Feb 73

With several notable exceptions, interest in the area of multiple molecular forms of phosphodiesterase remained relatively dormant during the decade following Thompson's discovery of more than one phosphodiesterase in brain in 1971. Within the last several years, however, over 20 novel agents have been identified that exert selective inhibitory effects on the various molecular forms of phosphodiesterase present within different cells. In addition, several studies have documented that such agents can produce discrete changes in cyclic AMP and cyclic GMP, an action that is not shared by "first generation" phosphodiesterase inhibitors such as theophylline. The purpose of this Perspective is to provide some clarity to this rapidly evolving area of selective phosphodiesterase inhibitors. Thus, we have attempted to characterize the different forms of phosphodiesterase present in various tissues and cells according to their kinetic properties, substrate specificity, etc. and also to characterize those major classes of agents that have been shown to inhibit phosphodiesterase activity, whether selectively or nonselectively. In addition, we have described several therapeutic areas wherein selective phosphodiesterase inhibitors might prove efficacious, paying particular attention to those areas in which selective phosphodiesterase inhibitors have already been shown to exert beneficial effects, namely, stimulation of myocardial contractility, inhibition of mediator release, and inhibition of platelet aggregation. Although focusing on these three areas, it is obvious that the potential therapeutic utility of selective phosphodiesterase inhibitors could conceivably extend to several other areas in which modulation of cyclic nucleotides can have desirable effects, including cancer chemotherapy, analgesia, the treatment of depression, Parkinson's disease, and learning and memory disorders. For example, the selective type III phosphodiesterase inhibitor rolipram has been shown to antagonize reserpine-induced hypothermia and also to potentiate yohimbine lethality, two tests that are indicative of antidepressant activity. In addition, microinjection of the selective PDE III inhibitor Ro 20-1724 into the rat brain stem has been shown to produce analgesia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A new generation of phosphodiesterase inhibitors: multiple molecular forms of phosphodiesterase and the potential for drug selectivity. 298 81

A clinical trial of the combination of naloxone in a low dose (1-1.5 micrograms X kg-1 body weight) with physostigmine (0.5-1.0 mg i.v.) was made to elucidate whether this combination could reverse postanaesthetic overdosing in neurosurgical patients without increasing postoperative pain. The investigation was made following previous findings that physostigmine has analgesic properties in addition to its systemic antisedative and anticholinergic effects as well as a stimulatory effect on morphine-depressed ventilation. Altogether 198 neurosurgical patients were investigated. The results showed that postanaesthetic over-sedation can be safely treated by a combination of naloxone and physostigmine in the dosages named above, resulting in the rapid reversal of sedation, where opiates, neuroleptics and benzodiazepines have been used. In contrast, this combination has very little effect on sedation following the administration of agents such as halothane and isoflurane. In the great majority of patients (95%), the treatment resulted in excellent analgesia during the first postoperative hour. The incidence of nausea and vomiting was increased somewhat by this treatment, but these side-effects could be minimized by decreasing the rate of drug administration. Physostigmine is contra-indicated in patients having symptoms and signs similar to those of Parkinson's disease, and the dose of physostigmine should also be reduced to 0.5 mg i.v. in all patients over the age of 65.
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PMID:Reversal of sedation and respiratory depression after anaesthesia by the combined use of physostigmine and naloxone in neurosurgical patients. 376 92

A case of Parkinson's Disease in a woman of 60 years, who developed a dependence on levodopa is presented. The psychic effects reported by the patient were sedation, sleep inducement, and analgesia.
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PMID:Levodopa dependence: a case report. 647 8

Hip fractures in patients with Parkinson's syndrome present a continuing challenge to orthopaedic surgeons. Sixty-two consecutive such patients have been reviewed. With or without operation, there was very high rate of mortality (31%) and complications. However, the functional results, the ability to walk, progression of the disability, and the quality of life were significantly better after operation. The results suggest that operation is the preferable solution for these patients. They require, however, much more particular care than other patients with hip fractures. This includes adequate adjusted antiparkinson medication, appropriate anesthesia with special attention to adequate ventilation and postoperative analgesia, more intensive respiratory and functional physiotherapy, very meticulous nursing care, and a relatively extended period of preventive antibiotics.
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PMID:Hip fractures in patients with Parkinson's syndrome. 682 45

Incubation of highly enriched neurons from rat cerebral cortex with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 for 18 h results in fragmentation of DNA at internucleosomal linkers, a feature of apoptosis. We report that neurons respond to exposure to gp120 with an increased release of arachidonic acid via activation of phospholipase A2. This process is not inhibited by antagonists of the N-methyl-D-aspartate (NMDA) receptor channels. To investigate the influence of arachidonic acid on the sensitivity of NMDA receptor towards its against, low concentrations of NMDA were coadministered with arachidonic acid. Under these conditions the NMDA-mediated cytotoxicity was enhanced. We conclude that gp120 causes an activation of phospholipase A2, resulting in an increased release of arachidonic acid which in turn sensitizes the NMDA receptor. Two compounds were found to act cytoprotectively against the deleterious effect caused by gp120 on neurons: Memantine [1-amino-3,5-dimethyladamantane] and Flupirtine [2-amino-3-ethoxycarbonylamino-6-(4-fluoro-benzyl-amino)-pyridine maleate]. Both compounds have been found to display a potent cytoprotective effect on neurons treated with the excitatory amino acid NMDA or with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120. The NMDA antagonist Memantine, a drug currently used in the therapy of spasticity and Parkinson's disease, prevented the effects of gp120 at micromolar concentrations. Flupirtine was previously found to be a centrally acting, nonopiate analgesic agent which additionally possesses anticonvulsant and muscle-relaxant activity at doses similar to those producing analgesia. The cytoprotective effect of Flupirtine in vitro was significant (above 10 microM). Considering the fact that both Memantine and Flupirtine display almost no clinical side effects, these drugs may prove useful both in preventing primary infection of brain cells with the HIV virus, as well as in treating the neurological disorders often associated with the immunodeficiency syndrome such as AIDS-related dementia.
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PMID:Neurotoxicity in rat cortical cells caused by N-methyl-D-aspartate (NMDA) and gp120 of HIV-1: induction and pharmacological intervention. 882 91

Neuronal nicotinic acetylcholine receptors (NAChRs) are pentameric ligand-gated ion channel receptors which exist as different functional subunit combinations which apparently subserve different physiological functions as indicated by molecular biological and pharmacological techniques. It is possible to design and synthesize novel compounds that have greater selective affinities and efficacies than nicotine for different NAChRs, which should translate into different behavioral profiles and therapeutic potentials. Examples of NAChR agonists studied are nicotine, SIB-1508Y, SIB-1553A and epibatidine. These compounds have different degrees of selectivity for human recombinant NAChRs, different neurotransmitter release profiles in vitro and in vivo and differential behavioral profiles. Preclinical studies suggest that SIB-1508Y is a candidate for the treatment of the motor and cognitive deficits of Parkinson's disease, whereas SIB-1553A appears to have potential as a candidate for the treatment of Alzheimer's disease. Epibatidine has a strong analgesic profile, however the ratio between pharmacological activity and undesirable effects is so low that it is difficult to envisage the use of this compound therapeutically. Nicotine has a broad profile of pharmacological activity, for instance demonstrating activity in models for cognition and analgesia. As for epibatidine, the adverse effects of nicotine severely limits its therapeutic use in humans. The discovery of subtype-selective NAChR agonists such as SIB-1508Y and SIB-1553A provides a new class of neuropsychopharmacological agents with better therapeutic ratios than nonspecific agents such as nicotine.
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PMID:The potential of subtype-selective neuronal nicotinic acetylcholine receptor agonists as therapeutic agents. 958 43

The treatment of patients suffering from chronic neuropathic pain remains a clinical challenge, particularly in cases where opioid therapy fails to provide sufficient pain relief. Spinal sensitization might be one cause for induction and maintenance of such states of pain, frequently accompainied by symptoms like allodynia, hyperalgesia and temporal summation of second pain. Experimental data concerning the role of NMDA-mediated processes in central sensitization and the effects of NMDA receptor antagonists in different models of neuropathic pain are reviewed. In clinical trials ketamine and other NMDA receptor blocking agents caused a significant reduction of hypersensitive states of pain, but nearly all authors described psychomimetic and other side effects. Aminoadamantanes like memantine and amantadine also have NMDA blocking properties and are widely used in the treatment of Parkinson's disease. Further clinical studies may reveal whether these substances will play a role as adjuncts in future pain treatment. Improving the efficacy of opioids by blocking NMDA receptor-mediated activity constitutes another clinically relevant concept for pain management. Numerous experiments have shown synergistic effects of NMDA antagonists and opioids in analgesia, while the development of opioid tolerance was prevented.
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PMID:[NMDA-receptor antagonist in pain therapy]. 974 42

Muscarinic acetylcholine receptors (M(1)-M(5)) regulate many key functions of the central and peripheral nervous system. Primarily because of the lack of receptor subtype-selective ligands, the precise physiological roles of the individual muscarinic receptor subtypes remain to be elucidated. Interestingly, the M(4) receptor subtype is expressed abundantly in the striatum and various other forebrain regions. To study its potential role in the regulation of locomotor activity and other central functions, we used gene-targeting technology to create mice that lack functional M(4) receptors. Pharmacologic analysis of M(4) receptor-deficient mice indicated that M(4) receptors are not required for muscarinic receptor-mediated analgesia, tremor, hypothermia, and salivation. Strikingly, M(4) receptor-deficient mice showed an increase in basal locomotor activity and greatly enhanced locomotor responses (as compared with their wild-type littermates) after activation of D1 dopamine receptors. These results indicate that M(4) receptors exert inhibitory control on D1 receptor-mediated locomotor stimulation, probably at the level of striatal projection neurons where the two receptors are coexpressed at high levels. Our findings offer new perspectives for the treatment of Parkinson's disease and other movement disorders that are characterized by an imbalance between muscarinic cholinergic and dopaminergic neurotransmission.
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PMID:Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M(4) muscarinic acetylcholine receptor knockout mice. 1053


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