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)

Amantadine and the analogue rimantadine have an antiviral effect on influenza A virus and are approximately 60% effective in preventing illness. The drugs are administered orally, and peak plasma concentration is achieved at two hours after a single dose. Side effects occur in 5-20% of the cases, but generally mild and transient and seen mainly with doses of more than 200 mg a day. This paper describes the mechanism of action and the pharmacokinetics of the drugs, and refers to some important clinical trials. Amantadine has been used in Norway to treat Parkinson's disease since 1972. The licensing of the amantadine and rimantadine for use against influenza A in this country is also discussed.
 ...
PMID:[Amantadine and rimantadine against influenza A]. 152 33

The anti-viral drug amantadine is used in the treatment of Parkinson's disease without the drug having a well established mechanism of action. Amantadine is reported to displace the non-competitive NMDA receptor antagonist MK-801 from its binding site in the central nervous system. We show that amantadine inhibits, in a non-competitive way, the NMDA receptor-mediated stimulation of acetylcholine release from rat neostriatum in vitro in 'therapeutic' (i.e. low micromolar range) concentrations. Moreover, contrary to previous reports, amantadine, in this concentration range, did not affect the in vitro release of dopamine from neostriatal tissue.
 ...
PMID:The anti-parkinsonian drug amantadine inhibits the N-methyl-D-aspartic acid-evoked release of acetylcholine from rat neostriatum in a non-competitive way. 161 82

Amantadine, a well-known antiviral agent, causing an increase in dopamine synthesis, release and the inhibition of re-uptake of noradrenaline and dopamine in central and peripheral catecholaminergic neurons, is successfully used in the treatment of Parkinson's disease. In the present paper, we have studied the effect of various doses of amantadine on in vivo prolactin secretion and the incorporation of 3H-thymidine and 3H-spiperone binding by the anterior pituitary gland of long-term diethylstilboestrol-treated male Wistar rats. Four weeks after a subcutaneous implantation of Silastic tubes containing 10 mg of diethylstilboestrol, a dramatic rise in serum prolactin levels was observed, accompanied by an increased uptake of 3H-thymidine by DNA anterior pituitary cells. Amantadine, given in the subcutaneous doses of 50, 5 and 0.5 mg/kg of body weight attenuated the stimulatory effect of stilboestrol on serum prolactin concentration in a dose-dependent fashion. On the other hand, the incorporation of 3H-thymidine into DNA pituitary cells in all the groups of amantadine-treated rats was only slightly suppressed. In an additional experiment, Scatchard analyses were performed on the in vitro 3H-spiperone binding kinetics in a dispersed anterior pituitary cell culture prepared from the pituitaries of 6-week diethylstilboestrol-treated rats. It has been found that amantadine injected in the dose of 5 mg/kg of body weight for 14 days induced a twofold decrease in the density of dopamine D2 binding sites (36.6 +/- 9.4 vs. 70.3 +/- 3.4 fmol/10(6) cells; p less than 0.02), while the apparent affinity of the receptors was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of amantadine on prolactin secretion, pituitary DNA synthesis and 3H-spiperone binding in male estrogen-treated rats. 214 19

We recently demonstrated that when different drugs (mainly used for the treatment of Parkinson's disease) are administered in combination they interfere with the availability of bromocriptine in the brain of rats (striatum and hypothalamus). In the present study performed with parkinsonian patients, we measured plasma levels of bromocriptine (RIA) over 4 h after giving orally 5 mg bromocriptine alone; together with levodopa 250 mg plus 25 mg DCI (10 patients); with 100 mg amantadine HCl (5 patients) and with biperiden 5 mg (5 patients). Amantadine and biperiden did not interfere with the pharmacokinetics of bromocriptine. However, levodopa significantly diminished plasma levels (a mean increment of 1.78 mg +/- 0.30 vs 0.92 +/- 0.18 mg/ml). We postulate that levodopa may interfere with the metabolism of bromocriptine in the liver. Although we did not observe substantial clinical differences among the patients (Webster scale), this study supports our previous findings and suggests that one of the advantages of combined treatment may result from a modification of the plasma levels of bromocriptine by levodopa. A "smoothing" of the plasma bromocriptine curve possibly avoids sudden oscillations of the drug availability and enables a more "stable" penetrability of the medication into the central nervous system.
 ...
PMID:Bromocriptine blood levels after the concomitant administration of levodopa, amantadine and biperiden in Parkinson's disease. 237 43

Intravenous administration of amantadine has been shown to be a quick-acting and highly effective method of treating patients with Parkinson's disease. The duration of this therapeutic effect during long-term oral treatment has, however, remained controversial. Therefore, the effect of intravenous treatment was compared with long-term oral treatment over a period of 6 months. Clinical scores and psychometrically determined dexterity improved significantly during 10-day infusion therapy (200 mg amantadine sulphate/day). This improvement was successfully maintained by oral treatment (600 mg/day). A decrease in effectiveness was not observed. Reaction times were within the normal range for the age group involved and did not change significantly during the course of the study. Amantadine serum concentration during the infusion period ranged between 500 and 1000 micrograms/l and produced values nearly half as high as those obtained during oral treatment (600 mg/day). There was a constant relationship (quotient: 1.3) between serum and cerebrospinal fluid concentration. Considerable inter-individual variations were noted. A significant inter-individual correlation between serum concentration and clinical and psychological improvement was not discernible.
 ...
PMID:Amantadine sulphate in treating Parkinson's disease: clinical effects, psychometric tests and serum concentrations. 270 63

Amantadine is one of the most commonly used drugs for the control of tremor in Parkinson's disease. Additionally, it has an antiviral action in the prevention of type A influenza. It has been previously reported that amantadine is nearly completely eliminated in the urine. No metabolites have been detected. Surprisingly, in a case of amantadine overdose, several metabolites could be identified by gas chromatography/mas spectrometry. This finding prompted us to re-investigate the metabolism of amantadine under a therapeutic dosing regimen. The bulk of the dose was eliminated unchanged. However, eight metabolites could be identified. Besides N-acetylation which is the major metabolic pathway, several rather unusual metabolic pathways were observed: N-methylation, formation of Schiff bases and N-formiates. No metabolites with a hydroxylated adamantane ring system could be detected.
 ...
PMID:A revision of the metabolic disposition of amantadine. 293 78

Amantadine is a drug with diverse uses ranging from prevention of influenza A illness to the treatment of patients with Parkinson's disease. It is available only in oral formulations from which it is well absorbed and widely distributed, little drug being present in the circulation. Apparent volume of distribution is inversely related to dose over the therapeutic range and accounts in part for a noteworthy logarithmic increase in plasma concentration as a function of dose. Elimination is primarily by renal clearance by both glomerular filtration and tubular secretion. Amantadine accumulates in patients with renal dysfunction. Hence, doses must be reduced in such patients to avoid toxicity. Interactions with other drugs appear uncommon. Relationships have been demonstrated between amantadine therapeutic effects and plasma concentrations in different study cohorts, but not in individual patients. Dose schedules have been suggested for individuals in whom amantadine kinetics are different from healthy subjects. However, these schedules are controversial in their choice of target concentrations and in being untested as to predictive value.
 ...
PMID:Clinical pharmacokinetics of amantadine hydrochloride. 328 Feb 12

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.
 ...
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.
 ...
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.
 ...
PMID:Pharmacologic treatment of parkinsonian tremor. 394 48


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>