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)

Of the neurological disorders, none can claim a battery of therapeutic agents based upon as rational a pharmacology as can Parkinson's disease. In this review, the clinical pharmacokinetics of the major classes of anti-Parkinsonian drugs is discussed. Although they are the oldest drugs in the anti-Parkinsonian armamentarium, little pharmacokinetic data are available regarding the anticholinergic and antihistaminic agents. Based on elimination half-lives of 10 to 18 hours, most could probably be effectively given on a twice-daily schedule. Amantadine is unique among anti-Parkinsonian agents both in lacking a clearly defined mechanism of action and in being eliminated from the body exclusively by renal excretion of unchanged drug. Thus the normal decline of renal function in the elderly Parkinsonian population becomes an important factor in avoiding potential drug toxicity. The pharmacokinetics and pharmacodynamics of levodopa are complex. Since it is an amino acid, it follows metabolic pathways and must compete for absorption and brain uptake with a number of large neutral amino acids. It has a short elimination half-life and, as Parkinson's disease progresses, the brain loses its capacity to store the drug and becomes dependent in a moment-to-moment fashion on plasma levodopa concentrations, creating therapeutic response fluctuations in over 50% of patients. Pharmacokinetic considerations in the management of these response fluctuations are discussed. The newest class of anti-Parkinsonian agents are the direct acting dopamine receptor agonists. These drugs, all derivatives of ergot, have more prolonged durations of anti-Parkinsonian action than levodopa. However, other than bromocriptine, clinical experience with members of this class of drugs is still limited.
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PMID:Clinical pharmacokinetics of anti-parkinsonian drugs. 331 29

Bromocriptine (2-Br-alpha-ergocryptine), a partial ergoline derivative, is a dopamine agonist which has been used successfully in the treatment of hyperprolactinemia, acromegaly and Parkinson's disease. The main targets for the action of the drug are the hypothalamic, hypophyseal pathway and the striatum. These regions contain different populations of neurons which interact with each other in a complex way. In order to check the mechanism of these interactions in rats, we administered different neuroactive drugs together with bromocriptine. After a single intraperitoneal injection, bromocriptine concentration in the striatum was 13.1 +/- 2.9 ng/mg protein, and in the hypothalamus 13.9 +/- 0.8 ng/mg protein. The largest increase in the bromocriptine content in the striatum was found after the concomitant administration of naloxone, an opiate receptor blocker (21.2 +/- 2.5 ng/mg protein). The largest increase of the bromocriptine content in the hypothalamus was found after the concomitant injection of methysergide, a serotonin receptor blocker (27.8 +/- 2.6 ng/mg protein). Amantadine, diazepam and haloperidol caused the largest decrease in the two regions. The mechanism of interaction and therapeutic implication of these findings are discussed.
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PMID:Selective regional effect of various neuroactive drugs on bromocriptine concentration in the brain of rats. 381 35

The relative efficacy of trihexiphenidyl hydrochloride, amantadine hydrochloride, and low-dose carbidopa-levodopa in reducing parkinsonian tremor was investigated using objective techniques. Trihexiphenidyl and carbidopa-levodopa decreased tremor by greater than 50%. Some patients responded to one drug but not to the other. Amantadine decreased tremor less than 25%. Monotherapy with trihexiphenidyl or carbidopa-levodopa should be the initial treatment for the tremor of Parkinson's disease.
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PMID:Pharmacologic treatment of parkinsonian tremor. 394 48

Fourteen slightly disabled patients with Parkinsonism were treated separately with benzhexol, amantadine, and levodopa. Benzhexol and amantadine both gave a 15% reduction in functional disability and levodopa a 36% reduction. Benzhexol lessened the rigidity and improved the flexion of posture of Parkinson's disease, but had little or no effect on akinesia and tremor. Amantadine and levodopa caused improvement in all these symptoms. The combination of benzhexol and amantadine was as effective after four weeks of treatment as levodopa was after six months.
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PMID:Comparative trial of benzhexol, amantadine, and levodopa in the treatment of Parkinson's disease. 483 13

A double-blind cross-over study was carried out in 54 patients with Parkinson's disease to evaluate the efficacy of amantadine hydrochloride as compared to a lactose placebo in the management of this illness. Amantadine proved to be a useful and safe addition to the armamentarium when given in daily doses of 200 mg. Forty-eight per cent of patients experienced moderate to good results while 31% showed no measurable improvement. The quality of the improvement was inferior to that obtained with levodopa, but the side effects were fewer. The study could not demonstrate a useful synergistic action between the two drugs, nor could the response to amantadine be used to predict that with levodopa. On the other hand, the addition of amantadine was useful in a few instances where optimal therapeutic doses of levodopa could not be given because of side effects. The mechanism of action of amantadine is still conjectural, but there is strong evidence to indicate some interaction with central dopamine metabolism.
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PMID:Amantadine-HCl (Symmetrel) in the management of Parkinson's disease: a double-blind cross-over study. 493 44

Parkinson's disease is an illness occurring in the third stage of life. At times, the patient suffers from arteriosclerosis as well. Reconstruction processes caused by aging are under way in the brain, which affect, among others, the synapses and transmitter substances. The biotransformation of medication may be changed in elderly persons. The tendency to multimorbidity leads to consumption of several drugs at the same time, possibly causing interference symptoms. Changes in transmitter balance and receptor excitability are, however, the main causes of the toxic side-effects of anti Parkinson therapy. The greater the nigrostriatal degeneration, the lower the tolerance level. Recently, in addition to basic therapy consisting of reduced doses of combined dopa preparations and/or Amantadine sulphate, dopaminergic agonists are used, which act on the receptors which have been maintained. This prevents some side-effects and stabilizes the patient's unpleasant daily fluctuations. Reducing the dosage prevents dyskinesia. pharmacotoxic psychoses require neuroleptics of the Thiaxanthen group or change-over to i.v. Amantadine sulphate infusions or Lisuride i.v.
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PMID:[Toxic drug effects of antiparkinson therapy and their preventability]. 652 82

The effects of anticholinergic and dopaminergic drugs used for Parkinson's disease were studied on the tremor induced by physostigmine (0.3-3.0 mg/kg) in rats. For the measurement of tremor a new electronic device was employed. Atropine (0.3-1.2 mg/kg) and biperiden (0.01-1.0 mg/kg) reduced the physostigmine-induced tremor in a dose-related manner and could abolish it. Biperiden was less potent than atropine. Methylatropine in a dose of 1.2 mg/kg slightly inhibited the tremor. Amantadine (0.3-3.0 mg/kg) reduced the tremor but only to a certain degree. Bromocriptine (0.1-10.0 mg/kg) reduced it in a manner that was not dose-related. Pimozide potentiated the tremor in the dose of 0.2 mg/kg but not in larger doses. At the onset of the tremor, a small decrease in rectal temperature occurred. The hypothermia lasted significantly longer than the tremor. Neither the anticholinergic nor the dopaminergic anti-Parkinson drugs altered the hypothermic effect of physostigmine. The results show that those anti-Parkinson drugs, which act by increasing the dopaminergic activity can counteract the tremor induced by physostigmine. However, these drugs are clearly less active than th anticholinergic anti-Parkinson drugs.
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PMID:Drugs for Parkinson's disease reduce tremor induced by physostigmine. 662 15

Amantadine is useful for the prevention and treatment of influenza A and for the treatment of Parkinson's disease and drug-induced extrapyramidal disorders. We have compared the pharmacokinetics of amantadine in patients with impaired or negligible renal function to that in normal subjects. The half-life of elimination in subjects with normal renal function was 11.8 +/- 2.1 hours (range, 9.7 to 14.5 h). Eight patients with various degrees of renal insufficiency (creatinine clearance from 43.1 to 5.9 mL/min . 1.73 m2) had half-lives of elimination from 18.5 h to 33.8 days. We also studied 10 patients on thrice-weekly hemodialysis. Assuming complete bioavailability of the drug, less than 5% of the dose was removed by each 4-hour hemodialysis. The mean half-life of elimination during chronic hemodialysis was 8.3 days (range, 7.0 to 10.3). We present guidelines for use of amantadine in patients with impaired renal function, including those on maintenance hemodialysis.
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PMID:Pharmacokinetics of amantadine hydrochloride in subjects with normal and impaired renal function. 721 1

Patients with Parkinson's disease were treated with different antiparkinsonian drugs and the amino acid levels in serum and cerebrospinal fluid were determined. Results obtained in 43 patients (L-dopa [26]; prodipine [6]; amantadine [11]) are reported. All drugs investigated produced an increase in amino acids in serum and in CSF, this enhancement being most pronounced for neutral, long-chain amino acids. Amantadine, however, showed this effect for a short period, only. Our results lead us to assume that this increased pool of amino acids in the CSF facilities the biosynthesis of amines with transmitter function from their precursor amino acids.
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PMID:[Comparison between the effects of L-dopa, prodipine and amantadine on the serum and CSF amino acid levels in Parkinson's disease (author's transl)]. 722 2

The authors report the results of treatment of hereditary extrapyramidal diseases with new preparations acting upon neurotransmitter systems. Patients with torsion dystonia, Huntington's chorea, Parkinson's disease, hereditary tremor, myoclonic epilepsy were followed-up for several years.. The best results in akinetic-rigidity syndromes (Parkinson's disease, rigid froms of torsion dystonia, Hallevorden-Spatz disease) were obtained with L-DOPA (including Sinemet, Nacom, Madopar) and in many patients these preparations were given in combination with other drugs (cholinolytic agents, Midantan) which contributed to compensation of the disturbed equilibrium of neurotransmitter systems and reduction of side effects. For decreasing the side effects of L-DOPA (hyperkineses of dystonic type, chorea and myoclonia) preparations from the group of phenothiazine and diazepine were given. In many cases improvement was achieved by slover increase of L-DOPA doses. In the hyperkinetic syndromes (Huntington's chorea, idiopathic tremor, myoclonic epilepsy, hyperkinetic torsion dystonia) preparations of phenothiazine, butyrophenone and new drugs active on the GABAergic system (Baclophen, Lyoresal, Pantogam) and diazepine (Clonazepam) were used. The analysis of the results shows that disturbed equilibrium of central neurotransmitters plays and important role in the pathogenesis of hereditary extrapyramidal system diseases.
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PMID:[Pathogenetic treatment of various hereditary extrapyramidal disorders with new drugs]. 732 7


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