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Identification
Name Primidone
Accession Number DB00794 (APRD00549)
Type small molecule
Groups approved
Description

An antiepileptic agent related to the barbiturates; it is partly metabolized to phenobarbital in the body and owes some of its actions to this metabolite. Adverse effects are reported to be more frequent than with phenobarbital. (From Martindale, The Extra Pharmacopoeia, 30th ed, p309)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Apo-Primidone
  • Cyral
  • Desoxyphenobarbitone
  • Hexadiona
  • Hexamidine
  • Lepimidin
  • Lepsiral
  • Liskantin
  • Majsolin
  • Medi-Pets
  • Midone
  • Milepsin
  • Misodine
  • Misolyne
  • Mizodin
  • Mizolin
  • Myidone
  • Mylepsin
  • Mylepsinum
  • Mysedon
  • Mysoline
  • Neurosyn
  • Pms Primidone
  • Prilepsin
  • Primacione
  • Primaclone
  • Primacone
  • Primakton
  • Primidon
  • Primidone Methanol Solution
  • Primoline
  • Prysoline
  • Pyrimidone "Medi-Pets"
  • Pyrimidone Medi-Pets
  • Resimatil
  • Sertan
Brand name mixtures Not Available
Categories
  • Anticonvulsants
  • Barbiturates
CAS number 125-33-7
Weight Average: 218.2518
Monoisotopic: 218.105527702
Chemical Formula C12H14N2O2
InChI Key InChIKey=DQMZLTXERSFNPB-UHFFFAOYSA-N
InChI
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)
Plain Text
IUPAC Name
5-ethyl-5-phenyl-1,3-diazinane-4,6-dione
SMILES
CCC1(C(=O)NCNC1=O)C1=CC=CC=C1
Plain Text
Mass Spec show (9 KB)
Taxonomy
Kingdom Organic
Classes
  • Barbiturates
  • Phenethylamines
  • Lactams
Substructures
  • Barbiturates
  • Carbonyl Compounds
  • Amino Ketones
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Aminals and Derivatives
  • Pyrimidines and Derivatives
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Lactams
Pharmacology
Indication For the treatment of epilepsy
Pharmacodynamics Primidone is a barbiturate with anticonvulsant properties. Primidone, either alone or used 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. Primidone raises electro- or chemoshock seizure thresholds or alters seizure patterns in experimental animals. Primidone per se has anticonvulsant activity as do its two metabolites, phenobarbital and phenylethylmalonamide (PEMA). In addition to its anticonvulsant activity, Primidone potentiates that of phenobarbital in experimental animals.
Mechanism of action Primidone is a GABA receptor agonist. The mechanism of Primidone's antiepileptic action is not known.
Absorption 90 to 100%
Volume of distribution Not Available
Protein binding 70%
Metabolism

Hepatic

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 2C19 Phenobarbital 0 0
Route of elimination Not Available
Half life 3-23 hours
Clearance Not Available
Toxicity Symptoms of an overdose typically include sluggishness, incoordination, difficulty in thinking, slowness of speech, faulty judgment, drowsiness or coma, shallow breathing, staggering, and in severe cases coma and death.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Xcel pharmaceuticals
  • Valeant pharmaceuticals international
  • Amneal pharmaceutical
  • Dr reddys laboratories ltd
  • Impax laboratories inc
  • Lannett co inc
  • Mutual pharmaceutical co inc
  • Vintage pharmaceuticals inc
  • Watson laboratories inc
  • West ward pharmaceutical corp
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Primidone powder 10.56 USD g
Mysoline 250 mg tablet 6.52 USD tablet
Mysoline 50 mg tablet 1.26 USD tablet
Primidone 250 mg tablet 1.02 USD tablet
Primidone 50 mg tablet 0.51 USD tablet
Apo-Primidone 250 mg Tablet 0.09 USD tablet
Apo-Primidone 125 mg Tablet 0.06 USD tablet
Patents Not Available
Properties
State solid
Melting point 281.5 oC
Experimental Properties
Property Value Source
water solubility 500 mg/L PhysProp
logP 1.6 PhysProp
logS -2.64 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 1.04e+00 g/l ALOGPS
logP 0.62 ALOGPS
logP 1.12 ChemAxon Molconvert
logS -2.32 ALOGPS
pKa 11.62 ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 58.20 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 59.04 ChemAxon Molconvert
polarizability 22.44 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Murphy K, Delanty N: Primary Generalized Epilepsies. Curr Treat Options Neurol. 2000 Nov;2(6):527-542. Pubmed
  2. Kagitani-Shimono K, Imai K, Okamoto N, Ono J, Okada S: Unverricht-Lundborg disease with cystatin B gene abnormalities. Pediatr Neurol. 2002 Jan;26(1):55-60. Pubmed
  3. Brown GM, Stone GH, Rathbone MP: Primidone and rapid cycling affective disorders. Lancet. 1993 Oct 9;342(8876):925. Pubmed
  4. Schaffer LC, Schaffer CB, Caretto J: The use of primidone in the treatment of refractory bipolar disorder. Ann Clin Psychiatry. 1999 Jun;11(2):61-6. Pubmed
  5. Young MC, Hughes IA: Loss of therapeutic control in congenital adrenal hyperplasia due to interaction between dexamethasone and primidone. Acta Paediatr Scand. 1991 Jan;80(1):120-4. Pubmed
External Links
Resource Link
KEGG Drug D00474 Link_out
KEGG Compound C07371 Link_out
PubChem Compound 4909 Link_out
PubChem Substance 46507775 Link_out
ChemSpider 4740 Link_out
Therapeutic Targets Database DAP000678 Link_out
PharmGKB PA451105 Link_out
Drug Product Database 396761 Link_out
RxList http://www.rxlist.com/cgi/generic2/primid.htm Link_out
Drugs.com http://www.drugs.com/cdi/primidone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Primidone Link_out
ATC Codes
  • N03AA03
AHFS Codes
  • 28:12.04
PDB Entries Not Available
FDA label show (108.3 KB)
MSDS show (65.5 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Avoid high doses of caffeine.
  • Take with food to reduce gastric irritation.
Targets

1. Gamma-aminobutyric-acid receptor subunit alpha-1

Pharmacological action: yes
Actions: potentiator

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P14867 Link_out
Gene: GABRA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57. Pubmed
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed
  3. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  4. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  6. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  7. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

2. Gamma-aminobutyric-acid receptor subunit alpha-2

Pharmacological action: yes
Actions: potentiator

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P47869 Link_out
Gene: GABRA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed

3. Gamma-aminobutyric-acid receptor subunit alpha-3

Pharmacological action: yes
Actions: potentiator

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P34903 Link_out
Gene: GABRA3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed

4. Gamma-aminobutyric-acid receptor subunit alpha-4

Pharmacological action: yes
Actions: potentiator

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P48169 Link_out
Gene: GABRA4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed

5. Gamma-aminobutyric-acid receptor subunit alpha-5

Pharmacological action: yes
Actions: potentiator

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P31644 Link_out
Gene: GABRA5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed

6. Gamma-aminobutyric-acid receptor subunit alpha-6

Pharmacological action: yes
Actions: potentiator

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: Q16445 Link_out
Gene: GABRA6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed
  2. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed

7. Neuronal acetylcholine receptor subunit alpha-4

Pharmacological action: unknown
Actions: antagonist

After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane

Organism class: human
UniProt ID: P43681 Link_out
Gene: CHRNA4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Arias HR, Bhumireddy P: Anesthetics as chemical tools to study the structure and function of nicotinic acetylcholine receptors. Curr Protein Pept Sci. 2005 Oct;6(5):451-72. Pubmed
  3. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. Pubmed

8. Neuronal acetylcholine receptor subunit alpha-7

Pharmacological action: unknown
Actions: antagonist

After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane

Organism class: human
UniProt ID: P36544 Link_out
Gene: CHRNA7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Arias HR, Bhumireddy P: Anesthetics as chemical tools to study the structure and function of nicotinic acetylcholine receptors. Curr Protein Pept Sci. 2005 Oct;6(5):451-72. Pubmed
  3. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. Pubmed

9. Glutamate receptor 2

Pharmacological action: unknown
Actions: antagonist

Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds AMPA(quisqualate) > glutamate > kainate

Organism class: human
UniProt ID: P42262 Link_out
Gene: GRIA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. Pubmed

10. Glutamate receptor, ionotropic kainate 2

Pharmacological action: unknown
Actions: antagonist

L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. May be involved in the transmission of light information from the retina to the hypothalamus. This receptor binds domoate > kainate > quisqualate > 6-cyano-7-nitroquinoxaline-2,3-dione > L-glutamate = 6,7- dinitroquinoxaline-2,3-dione > dihydrokainate

Organism class: human
UniProt ID: Q13002 Link_out
Gene: GRIK2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. Pubmed
Enzymes

1. Cytochrome P450 2C19

Actions: substrate, inducer

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Application available online: The P450 Program
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C9

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A4

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 1A2

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2B6

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C8

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on October 20, 2011 17:36

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.