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Archives of Neurology Mar 1974
Topics: Amides; Biotransformation; Brain; Chromatography, Thin Layer; Crystallization; Electroencephalography; Evoked Potentials; Half-Life; Malonates; Neurologic Manifestations; Phenobarbital; Photic Stimulation; Poisoning; Primidone
PubMed: 4812959
DOI: 10.1001/archneur.1974.00490330063011 -
Journal of Neurology Jan 1988To clarify whether primidone itself, and not only its metabolite phenobarbitone, suppresses essential tremor, the effect of a high single dose of primidone was tested....
To clarify whether primidone itself, and not only its metabolite phenobarbitone, suppresses essential tremor, the effect of a high single dose of primidone was tested. Of 11 patients, 8 showed a reduction of their tremor by 54%-69% for up to 28 h. The serum concentration of primidone was as expected, whereas those of the metabolites phenyl-ethyl-malonamide and phenobarbitone were very low. The tremor suppression can thus be considered to be an effect of primidone. Three of the 11 patients did not show a reduction of tremor.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Phenobarbital; Phenylethylmalonamide; Primidone; Tremor
PubMed: 3367165
DOI: 10.1007/BF00314310 -
CMAJ : Canadian Medical Association... Nov 2017
Topics: Adrenergic beta-Antagonists; Aging; Essential Tremor; Humans; Primidone
PubMed: 29109210
DOI: 10.1503/cmaj.170128 -
Nederlands Tijdschrift Voor Geneeskunde Nov 2003The antiepileptic drug primidone is to be withdrawn from sale by January 2004. After this date, the drug will still be available for a time, but only on a limited basis.... (Review)
Review
The antiepileptic drug primidone is to be withdrawn from sale by January 2004. After this date, the drug will still be available for a time, but only on a limited basis. Most primidone users are elderly patients who have been prescribed this drug for many years. Changing to a new drug constitutes a health risk for them. If primidone treatment is discontinued too quickly, withdrawal seizures may appear, some of which may be severe. In patients who have not suffered an epileptic seizure for many years, discontinuing medication may be considered. Whenever continuation of anticonvulsive treatment is desirable, it may probably be a good idea to switch over to some newer antiepileptic drug. If a simple and quick substitution is essential, primidone may be replaced by its main metabolite: phenobarbital. General practitioners and neurologists are strongly advised to alter patients' medication in good time.
Topics: Anticonvulsants; Drug and Narcotic Control; Epilepsy; Humans; Phenobarbital; Primidone; Substance Withdrawal Syndrome
PubMed: 14669538
DOI: No ID Found -
The Journal of Pediatrics Oct 1984
Topics: Drug Therapy, Combination; Female; Humans; Infant; Male; Phenobarbital; Phenytoin; Primidone; Seizures
PubMed: 6481545
DOI: 10.1016/s0022-3476(84)80442-4 -
Medicina Clinica Jun 2024In the last decades there has been progress in the treatment of essential tremor (TE) especially in the surgical field and to a lesser extent in the pharmacological... (Review)
Review
In the last decades there has been progress in the treatment of essential tremor (TE) especially in the surgical field and to a lesser extent in the pharmacological field. We carry out a review of the currently available treatments. The first intervention is the use of non-pharmacological and non-surgical strategies (general advice, occupational therapy, speech therapy, psychotherapy). With discrete advances, the pharmacological treatment is not very satisfactory. Only 30-60% of patients have a positive response, and in these the anti-tremor effectiveness is 40-60%. The first-line drugs are still propranolol and primidone. In cases with severe tremor we will consider a surgical option, the method of choice being thalamotomy using high-intensity focused ultrasound. In the future we must continue to study the pathophysiology of TE, develop drugs specifically designed for TE and improve the technology of available invasive techniques.
Topics: Essential Tremor; Humans; Propranolol; Primidone; High-Intensity Focused Ultrasound Ablation; Anticonvulsants; Thalamus; Adrenergic beta-Antagonists
PubMed: 38553256
DOI: 10.1016/j.medcli.2023.12.013 -
Neurology Jan 1986Primidone, 50 to 1,000 mg/d, reduced the amplitude of essential tremor in both untreated and propranolol-treated patients. Low doses were as effective as high doses.... (Clinical Trial)
Clinical Trial
Primidone, 50 to 1,000 mg/d, reduced the amplitude of essential tremor in both untreated and propranolol-treated patients. Low doses were as effective as high doses. Primidone decreased tremor more than propranolol. There was no correlation between therapeutic response and serum levels. Acute reactions to the initial dose and side effects of higher doses caused drug intolerance. A single oral dose (250 mg) decreased tremor by 60% 1 to 7 hours after ingestion, with stable serum primidone levels but no detectable phenobarbital levels. Tremor control was lost when phenobarbital was substituted for primidone. Primidone is an effective agent for the treatment of essential tremor.
Topics: Dose-Response Relationship, Drug; Humans; Male; Middle Aged; Phenobarbital; Primidone; Propranolol; Tremor
PubMed: 3941767
DOI: 10.1212/wnl.36.1.121 -
British Medical Journal Sep 1954
Topics: Anticonvulsants; Epilepsy; Primidone
PubMed: 13190211
DOI: 10.1136/bmj.2.4888.625 -
Archives Internationales de... Nov 1979In dogs, the metabolism of primidone and the pharmacokinetics of the drug itself as well as its metabolites phenobarbital and phenylethylmalonic acid diamide (PEMA) was...
In dogs, the metabolism of primidone and the pharmacokinetics of the drug itself as well as its metabolites phenobarbital and phenylethylmalonic acid diamide (PEMA) was followed after single oral doses of 30 mg/kg (0.14 mmole/kg). Primidone was rapidly absorbed, so that maximal serum concentrations were reached after 2 hr, the concentration fell then with a half-life averaging 5 hr in Beagles and 10 hr in Mongrels. PEMA appeared in plasma with a ka of 0.003--0.005 min-1, reached maximal concentrations after about 6.5 hr in Beagles and 12 hr in Mongrels. The elimination half-life averaged 7.5 hr in Beagles and 14 hr in Mongrels. After single oral doses, phenobarbital could only be detected in low concentrations in some Beagles. Phenobarbital had an elimination half-life of 32 +/- 4.8 hr in Beagles and of 70 +/- 16 hr in Mongrels. During continued treatment with daily doses of 30--50 mg/kg primidone, steady-state concentrations of about 15 micrograms/ml (65 nmole/ml) were reached after 6--8 days, the PEMA concentrations showed rather pronounced fluctuations around average values of 8--10 micrograms/ml (39--49 nmole/ml), whereas the concentrations of primidone mainly remained below 5 micrograms/ml (23 nmole/ml). In mice, the anticonvulsant potency of the 3 drugs was determined: Elevations of the electroconvulsant threshold by 40 V were produced by 0.01 mmole/kg of phenobarbital, 0.017 mmole/kg of primidone or 0.37 mmole/kg of PEMA. Taking the anticonvulsant potency of the 3 drugs into consideration, phenobarbital is responsible for more than 85% of the total anticonvulsant activity during continued medication of primidone. The penetration of primidone and its metabolites into the cerebro-spinal fluid was followed: phenobarbital reached steady state levels already after 1--1.5 hr, primidone and PEMA not before 2.5 hr. The concentrations in CSF roughly corresponded to the free drug in plasma. On account of the similarities in metabolism and pharmacokinetics of primidone in dog and man, the former species seems to be a suitable model in epilepsy research. Differences between both species are most pronounced in the Beagle.
Topics: Animals; Anticonvulsants; Dogs; Female; Half-Life; Injections, Intravenous; Kinetics; Male; Phenobarbital; Primidone
PubMed: 543743
DOI: No ID Found -
Acta Neurologica Scandinavica May 1987Primidone was compared to the unselective beta adrenoceptor antagonist propranolol in the suppression of essential tremor. In a 4-week single-blind placebo-controlled... (Clinical Trial)
Clinical Trial Comparative Study
Primidone was compared to the unselective beta adrenoceptor antagonist propranolol in the suppression of essential tremor. In a 4-week single-blind placebo-controlled study primidone was given in increasing doses from 62.5 mg X 1 up to 250 mg X 3 daily and propranolol 20 mg X 3 daily. The drugs produced a similar reduction in the degree of tremor after 2 and 1 weeks' medication respectively. This indicates that primidone can be an alternative to propranolol when beta-blockers are contraindicated. However, primidone was significantly even more effective in the beginning after only 2 doses, when at the same time 10 of 13 patients showed a maximum of acute toxic side-effects producing nausea, vomiting, giddiness and/or sedation. Correlation analysis between the individual tremor amplitude reductions and plasma primidone concentrations showed on the second day a tendency towards a greater reduction in tremor in those patients with the highest primidone plasma concentration. By the fourteenth day tremor had increased compared with the second day and correlation analysis between individual increase in tremor amplitude and plasma phenobarbital concentrations showed the highest degree of tremor increase in those patients who had the highest levels of phenobarbital. These and other data suggest that after the first doses, tremor suppression and acute toxicity is related to the initial exposure to primidone and the plasma level of the drug itself rather than its metabolites phenobarbital and phenylethylmalanomide. The individual tremor frequency spectrums did not change significantly during the placebo and propranolol periods, whereas the frequency tended to decrease during the primidone period.
Topics: Adrenergic beta-Antagonists; Adult; Aged; Blood Pressure; Female; Heart Rate; Humans; Male; Middle Aged; Monitoring, Physiologic; Primidone; Propranolol; Tremor
PubMed: 2887081
DOI: 10.1111/j.1600-0404.1987.tb05455.x