U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C12H14N2O2
Molecular Weight 218.2522
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PRIMIDONE

SMILES

CCC1(c2ccccc2)C(=NCN=C1O)O

InChI

InChIKey=DQMZLTXERSFNPB-UHFFFAOYSA-N
InChI=1S/C12H14N2O2/c1-2-12(9-6-4-3-5-7-9)10(15)13-8-14-11(12)16/h3-7H,2,8H2,1H3,(H,13,15)(H,14,16)

HIDE SMILES / InChI

Molecular Formula C12H14N2O2
Molecular Weight 218.2522
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/?term=2871724 http://www.rxlist.com/mysoline-drug/side-effects-interactions.htm

Primidone is an anticonvulsant of the barbiturate class. It was introduced in 1954 under the brand name Mysoline by Wyeth in the United States. Mysoline, used alone or concomitantly with other anticonvulsants, is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy. Mysoline raises electro- or chemoshock seizure thresholds or alters seizure patterns in experimental animals. The mechanism(s) of primidone’s antiepileptic action is not known. Primidone per se has anticonvulsant activity, as do its two metabolites, phenobarbital and phenylethylmalonamide (PEMA). In addition to its anticonvulsant activity, PEMA potentiates the anticonvulsant activity of phenobarbital in experimental animals. Primidone itself doesn’t act on GABA-A receptors. It is active metabolite - phenobarbital primary acts via modulation of GABA -A receptors. The most frequently occurring early side effects are ataxia and vertigo. These tend to disappear with continued therapy, or with reduction of initial dosage. Occasionally, the following have been reported: nausea, anorexia, vomiting, fatigue, hyperirritability, emotional disturbances, sexual impotency, diplopia, nystagmus, drowsiness, and morbilliform skin eruptions.Granulocytopenia, agranulocytosis, and red-cell hypoplasia and aplasia, have been reported rarely. These and, occasionally, other persistant or severe side effects may necessitate withdrawal of the drug. Megaloblastic anemia may occur as a rare idiosyncrasy to Mysoline and to other anticonvulsants. The anemia responds to folic acid without necessity of discontinuing medication.

Originator

Curator's Comment:: The effectiveness of primidone was demonstrated by Yule Bogue in the Imperial Chemical Industries' Laboratories in 1949 and the results published in 1953.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
MYSOLINE

Approved Use

Mysoline, used alone or concomitantly with other anticonvulsants, is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy.

Launch Date

-4.99219202E11
Primary
MYSOLINE

Approved Use

Mysoline, used alone or concomitantly with other anticonvulsants, is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy.

Launch Date

-4.99219202E11
Primary
MYSOLINE

Approved Use

Mysoline, used alone or concomitantly with other anticonvulsants, is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy.

Launch Date

-4.99219202E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4.45 μg/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PRIMIDONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
140.5 μg × h/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PRIMIDONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
21.9 h
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PRIMIDONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
62.5 mg 1 times / day multiple, oral
Studied dose
Dose: 62.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 62.5 mg, 1 times / day
Sources: Page: p.316
unhealthy, 18-83
n = 19
Health Status: unhealthy
Condition: Essential tremor
Age Group: 18-83
Sex: M+F
Population Size: 19
Sources: Page: p.316
Disc. AE: Nausea, Ataxia...
AEs leading to
discontinuation/dose reduction:
Nausea (acute)
Ataxia (acute)
Dizziness (acute)
Confusion (acute)
Sources: Page: p.316
15 mg single, oral (max)
Overdose
Dose: 15 mg
Route: oral
Route: single
Dose: 15 mg
Sources:
healthy, 34
n = 1
Health Status: healthy
Age Group: 34
Sex: F
Population Size: 1
Sources:
Disc. AE: Coma, Crystalluria...
AEs leading to
discontinuation/dose reduction:
Coma
Crystalluria
Sources:
500 mg 4 times / day multiple, oral
Recommended
Dose: 500 mg, 4 times / day
Route: oral
Route: multiple
Dose: 500 mg, 4 times / day
Sources: Page: p.2
unhealthy
Health Status: unhealthy
Condition: Epileptic seizures
Sources: Page: p.2
Disc. AE: Suicidal behavior, Suicidal ideation...
AEs leading to
discontinuation/dose reduction:
Suicidal behavior
Suicidal ideation
Sources: Page: p.2
AEs

AEs

AESignificanceDosePopulation
Ataxia acute
Disc. AE
62.5 mg 1 times / day multiple, oral
Studied dose
Dose: 62.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 62.5 mg, 1 times / day
Sources: Page: p.316
unhealthy, 18-83
n = 19
Health Status: unhealthy
Condition: Essential tremor
Age Group: 18-83
Sex: M+F
Population Size: 19
Sources: Page: p.316
Confusion acute
Disc. AE
62.5 mg 1 times / day multiple, oral
Studied dose
Dose: 62.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 62.5 mg, 1 times / day
Sources: Page: p.316
unhealthy, 18-83
n = 19
Health Status: unhealthy
Condition: Essential tremor
Age Group: 18-83
Sex: M+F
Population Size: 19
Sources: Page: p.316
Dizziness acute
Disc. AE
62.5 mg 1 times / day multiple, oral
Studied dose
Dose: 62.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 62.5 mg, 1 times / day
Sources: Page: p.316
unhealthy, 18-83
n = 19
Health Status: unhealthy
Condition: Essential tremor
Age Group: 18-83
Sex: M+F
Population Size: 19
Sources: Page: p.316
Nausea acute
Disc. AE
62.5 mg 1 times / day multiple, oral
Studied dose
Dose: 62.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 62.5 mg, 1 times / day
Sources: Page: p.316
unhealthy, 18-83
n = 19
Health Status: unhealthy
Condition: Essential tremor
Age Group: 18-83
Sex: M+F
Population Size: 19
Sources: Page: p.316
Coma Disc. AE
15 mg single, oral (max)
Overdose
Dose: 15 mg
Route: oral
Route: single
Dose: 15 mg
Sources:
healthy, 34
n = 1
Health Status: healthy
Age Group: 34
Sex: F
Population Size: 1
Sources:
Crystalluria Disc. AE
15 mg single, oral (max)
Overdose
Dose: 15 mg
Route: oral
Route: single
Dose: 15 mg
Sources:
healthy, 34
n = 1
Health Status: healthy
Age Group: 34
Sex: F
Population Size: 1
Sources:
Suicidal behavior Disc. AE
500 mg 4 times / day multiple, oral
Recommended
Dose: 500 mg, 4 times / day
Route: oral
Route: multiple
Dose: 500 mg, 4 times / day
Sources: Page: p.2
unhealthy
Health Status: unhealthy
Condition: Epileptic seizures
Sources: Page: p.2
Suicidal ideation Disc. AE
500 mg 4 times / day multiple, oral
Recommended
Dose: 500 mg, 4 times / day
Route: oral
Route: multiple
Dose: 500 mg, 4 times / day
Sources: Page: p.2
unhealthy
Health Status: unhealthy
Condition: Epileptic seizures
Sources: Page: p.2
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no
no
no
no
unlikely
weak
yes [Activation 39.81072 uM]
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: The mean serum concentration of carbamazepine is lower when the drug is given in combination with primidone (58·2%) than when carbamazepine is given alone (100%).
Drug as victim
PubMed

PubMed

TitleDatePubMed
Prediction of adsorption from multicomponent solutions by activated carbon using single-solute parameters. Part II--Proposed equation.
2002
Fate of pharmaceuticals during indirect potable reuse.
2002
Treatment of epilepsy in women of reproductive age: pharmacokinetic considerations.
2002
Management of essential tremor.
2002 Jul
Clinical and electromyographic assessment of essential tremor treatment.
2002 Jun
Some common issues in the use of antiepileptic drugs.
2002 Mar
Primary standardization of assays for anticonvulsant drugs: comparison of accuracy and precision.
2002 Nov
Prolonged anticonvulsant hypersensitivity syndrome related to lamotrigine in a patient with human immunodeficiency virus.
2002 Nov-Dec
QT length and heart function in primidone hypocalcaemia.
2002 Oct
Benefits and risks of pharmacological treatments for essential tremor.
2003
Drug treatment of epilepsy in elderly people: focus on valproic Acid.
2003
Effects of barbiturates on human platelet aggregation differ depending on their chemical structures.
2003 Aug
Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs.
2003 Aug
Tremor.
2003 Aug
Essential tremor: differential diagnosis and current therapy.
2003 Aug 1
[Late compensation for a recalled drug].
2003 Dec 15
Effects of antiepileptic comedication on levetiracetam pharmacokinetics: a pooled analysis of data from randomized adjunctive therapy trials.
2003 Feb
Effects of concomitant antiepileptic drugs on serum carbamazepine concentration in epileptic patients: quantitative analysis based on extracellular water volume as a transforming factor.
2003 Jan
The absorption of gabapentin following high dose escalation.
2003 Jan
Simultaneous plasma lamotrigine analysis with carbamazepine, carbamazepine 10,11 epoxide, primidone, phenytoin, phenobarbital, and PEMA by micellar electrokinetic capillary chromatography (MECC).
2003 Jul-Aug
Tremor--easily seen but difficult to describe and treat.
2003 Mar
Microemulsion electrokinetic chromatography applied for separation of levetiracetam from other antiepileptic drugs in polypharmacy.
2003 Mar
The ideal pharmacokinetic properties of an antiepileptic drug: how close does levetiracetam come?
2003 May
[Oxcarbazepine induced interstitial nephritis in a patient with drug hypersensitivity syndrome].
2003 Nov 16-30
[Antiepileptic primidone shortly to be withdrawn from sale: change medication now].
2003 Nov 22
Low doses of topiramate are effective in essential tremor: a report of three cases.
2003 Nov-Dec
Sedation caused by primidone may exacerbate dementia.
2003 Oct
AstraZeneca postpones discontinuation of Mysoline.
2003 Oct
Use of primidone in low doses (250 mg/day) versus high doses (750 mg/day) in the management of essential tremor. Double-blind comparative study with one-year follow-up.
2003 Oct
Comparison of human exposures to selected chemicals with thresholds from NTP carcinogenicity studies in rodents.
2003 Sep
Essential tremor: diagnosis and treatment.
2003 Sep
Antiepileptic drug pharmacokinetics during pregnancy and lactation.
2003 Sep 1
Key structural features of ligands for activation of human pregnane X receptor.
2004 Apr
Fatal mix-up between prednisone and primidone.
2004 Aug 1
When breastfeeding mothers need CNS-acting drugs.
2004 Fall
[Drug interactions with antiepileptic agents].
2004 Feb 28
Natural history and syndromic associations of orthostatic tremor: a review of 41 patients.
2004 Jul
Levetiracetam in focal epilepsy and hepatic porphyria: a case report.
2004 May
Anticonvulsant efficacy of the low-affinity partial benzodiazepine receptor agonist ELB 138 in a dog seizure model and in epileptic dogs with spontaneously recurrent seizures.
2004 Oct
Pilot efficacy and tolerability: a randomized, placebo-controlled trial of levetiracetam for essential tremor.
2004 Oct
Simple and rapid micellar electrokinetic capillary chromatographic method for simultaneous determination of four antiepileptics in human serum.
2004 Oct
Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines.
2004 Oct
Essential tremor. Epidemiology, diagnosis, and treatment.
2004 Sep
Epilepsy in the United Kingdom: seizure frequency and severity, anti-epileptic drug utilization and impact on life in 1652 people with epilepsy.
2004 Sep
[Population pharmacokinetics of carbamazepine in adults with epilepsy].
2005 Jan-Feb
Drug-induced hypersensitivity syndrome in a premature infant.
2005 Jan-Feb
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology.
2005 Jun 28
Pharmacological treatment of disabling tremor.
2005 Mar
Primidone is associated with interictal depression in patients with epilepsy.
2005 May
Patents

Sample Use Guides

Patients 8 years of age and older who have received no previous treatment may be started according to the following regimen using either 50 mg or scored 250 mg tablets: Days 1 to 3: 100 to 125 mg at bedtime. Days 4 to 6: 100 to 125 mg b.i.d. Days 7 to 9: 100 to 125 mg t.i.d. Day 10 to maintenance: 250 mg t.i.d.
Route of Administration: Oral
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:05:20 UTC 2021
Edited
by admin
on Fri Jun 25 21:05:20 UTC 2021
Record UNII
13AFD7670Q
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PRIMIDONE
EP   GREEN BOOK   HSDB   INN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
INN  
Official Name English
PRIMIDONE [VANDF]
Common Name English
PRIMIDONE [INN]
Common Name English
4,6(1H,5H)-PYRIMIDINEDIONE, 5-ETHYLDIHYDRO-5-PHENYL-
Systematic Name English
PRIMIDONE [IARC]
Common Name English
PRIMACLONE
Common Name English
PRIMIDONE [MART.]
Common Name English
MYSOLINE
Brand Name English
PRIMIDONE [EP MONOGRAPH]
Common Name English
LEPIMIDIN
Common Name English
RESIMATIL
Common Name English
NSC-41701
Code English
PRIMIDONE [EP]
Common Name English
PRIMIDONE [HSDB]
Common Name English
PRIMIDONE [USP-RS]
Common Name English
PRIMIDONE [ORANGE BOOK]
Common Name English
PRIMIDONE [WHO-DD]
Common Name English
PRIMIDONE [USP MONOGRAPH]
Common Name English
5-ETHYLDIHYDRO-5-PHENYL-4,6(1H,5H)-PYRIMIDINEDIONE
Systematic Name English
PRIMIDONE [MI]
Common Name English
PRIMIDONE [GREEN BOOK]
Common Name English
PRIMIDONE [JAN]
Common Name English
Classification Tree Code System Code
WHO-VATC QN03AA03
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
NCI_THESAURUS C67084
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
WHO-ATC N03AA03
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
NDF-RT N0000008486
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
LIVERTOX 798
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
CFR 21 CFR 862.3680
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
NDF-RT N0000175753
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
NCI_THESAURUS C264
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
CFR 21 CFR 520.1900
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
Code System Code Type Description
IUPHAR
5338
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
EPA CompTox
125-33-7
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
DRUG BANK
DB00794
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
MERCK INDEX
M9135
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY Merck Index
PUBCHEM
4909
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
RXCUI
8691
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY RxNorm
EVMPD
SUB10045MIG
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
ECHA (EC/EINECS)
204-737-0
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
FDA UNII
13AFD7670Q
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
LACTMED
Primidone
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
ChEMBL
CHEMBL856
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
INN
248
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
WIKIPEDIA
PRIMIDONE
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
CAS
125-33-7
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
DRUG CENTRAL
2267
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
MESH
D011324
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
NCI_THESAURUS
C47686
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
HSDB
3169
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY
USP_CATALOG
1562000
Created by admin on Fri Jun 25 21:05:21 UTC 2021 , Edited by admin on Fri Jun 25 21:05:21 UTC 2021
PRIMARY USP-RS
Related Record Type Details
METABOLIC ENZYME -> INDUCER
BINDER->LIGAND
Related Record Type Details
METABOLITE -> PARENT
Metabolite to parent drug ratio in non-uraemic human plasma.
METABOLITE TO PARENT DRUG RATIO
PLASMA; URINE
METABOLITE -> PARENT
Metabolite to parent drug ratio in non-uraemic human plasma.
METABOLITE TO PARENT DRUG RATIO
PLASMA; URINE
METABOLITE -> PARENT
Percent of dose excreted in urine as metabolite. Primidone is converted in man to phenobarbitone.
AMOUNT EXCRETED
URINE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC Population
PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC Elimination
PHARMACOKINETIC
Elimination
PHARMACOKINETIC