ChemicalBook > Product Catalog > API > Nervous system drugs > Antiepileptic and anticonvulsant > Primidone
Primidone Chemical Properties
- Melting point:281-282°C
- Boiling point:358.94°C (rough estimate)
- Density 1.1402 (rough estimate)
- refractive index 1.6660 (estimate)
- Flash point:9℃
- storage temp. Sealed in dry,Room Temperature
- solubility Very slightly soluble in water, slightly soluble in ethanol (96 per cent). It dissolves in alkaline solutions.
- form neat
- Water Solubility <0.1 g/100 mL at 19 ºC
- Merck 14,7746
- CAS DataBase Reference125-33-7(CAS DataBase Reference)
- NIST Chemistry ReferencePrimidone(125-33-7)
- IARC2B (Vol. 108) 2016
- EPA Substance Registry SystemPrimidone (125-33-7)
Primidone Usage And Synthesis
- DescriptionPrimidone is chemically and structurally similar to phenobarbital with the exception that the carbonyl group on C2 is replaced by a methylene group. This modification leads to the production of a drug with strong anticonvulsant properties without expressed soporific effects.
- DescriptionPrimidone (Item No. 19277) is an analytical reference material categorized as a barbiturate that can be detected in urine.1 The physiological and toxicological properties of this compound are not known; however, it is presumed to be a modulator of GABAA receptors.2 This product is intended for research and forensic applications.
- Chemical PropertiesCrystalline Solid
- UsesPrimidone is mainly used for major attacks.
- UsesPrimidone is an Anticonvulsant.
- DefinitionChEBI: A pyrimidone that is dihydropyrimidine-4,6(1H,5H)-dione substituted by an ethyl and a phenyl group at position 5. It is used as an anticonvulsant for treatment of various types of seizures.
- brand nameMysoline (Valeant); Mysoline (Xcel).
- General DescriptionOdorless white crystalline powder. Slightly bitter taste. No acidic properties.
- Air & Water ReactionsInsoluble in water.
- Reactivity ProfilePrimidone is an amide. May react with azo and diazo compounds to generate toxic gases. May react with strong reducing agents to form flammable gases. A very weak base. The Combustion generates toxic mixed oxides of nitrogen (NOx).
- Fire HazardFlash point data for Primidone are not available; however, Primidone is probably combustible.
- Biological ActivityAnticonvulsant.
- PharmacokineticsApproximately 60 to 80% of an oral dose of primidone is absorbed and slowly metabolized by the liver to phenobarbital and phenylethylmalonamide (PEMA). All three molecules have antiseizure effects, but PEMA appears to be weaker and to
be the more toxic metabolite. During chronic therapy, approximately 15 to 25% of an oral dose of primidone is excreted in the
urine unchanged, 15 to 25% metabolized to phenobarbital, and 50 to 70% excreted as PEMA (half-life, 24–48 hours). The
phenobarbital metabolite may be excreted in the urine unchanged, as its p-hydroxy metabolite, and as glucuronide or sulfate
conjugates. Following an oral dose, the peak plasma levels for primidone are reached in approximately 4 hours, with a reported
half-life of 10 to 12 hours. Plasma concentrations in the range of 8 to 12 μg/mL control seizures and minimize adverse effects.
Primidone shows antiseizure activity before the phenobarbital levels reach therapeutic range. Only after chronic dosing of
primidone are the levels of phenobarbital significant, suggesting autoinduction. Serum levels of chronically administered
primidone exceed those of its metabolite, phenobarbital, thus demonstrating that it has antiseizure activity independent of
phenobarbital. When primidone is coadministered with enzyme-inducing AEDs, the levels of its phenobarbital metabolite may be
two- to threefold higher than those in the noninduced state. Protein binding of primidone and PEMA is negligible, and the
phenobarbital metabolite is approximately 50% protein bound.
Primidone use is associated with decreases in CBZ, lamotrigine, valproate, tiagabine, and zonisamide serum levels. Primidone levels are increased by nicotinamide and isoniazid. Hydantoins increase the plasma concentrations of primidone, phenobarbital, and PEMA. CBZ increases levels of phenobarbital derived from primidone. Primidone levels are decreased by succinimides, CBZ, and acetazolamide.
- Clinical UsePrimidone is the 2-deoxy derivative of phenobarbital and is approved by the U.S. FDA for initial or adjunctive treatment of simple partial, complex partial, and tonic-clonic seizures. It is less effective against these types of seizures than is phenytoin or CBZ, and it shares the antiseizure and sedative actions of phenobarbital. Although not approved for the purpose, it often is used to treat benign familial tremor (essential tremor).
- Side effectsAs with phenobarbital, serious toxicity for primidone is rare, although it may cause disabling sedation, irritability, and decreased mental functioning in a number of persons. Ataxia, dysphoria, idiosyncratic rash, leukopenia, agranulocytosis, lymphadenopathy, hepatitis, and a systemic lupus erythematosus–like syndrome have been reported adverse effects for primidone. Deficiencies of folic acid and of vitamins D and K are possible with long-term therapy of primidone, as is a folateresponsive megaloblastic anemia. Measurement of the complete blood cell count should be performed at 6-month intervals.
- Safety ProfilePoison by ingestion and intraperitoneal routes. Human teratogenic effects include developmental abnormalities of the craniofacial area, skin and skin appendages, and cardlovascular system. Human reproductive effects: effects on newborn, including unusual growth statistics, drug dependence, physical and other neonatal changes. Experimental teratogenic and reproductive effects. Human mutation data reported. An addictive drug. When heated to decomposition it emits toxic fumes of NOx. See also BARBITURATES.
- Chemical SynthesisPrimidone, 5-ethyl-5-phenylhexahydropyrimidinedione-4,6 (9.2.1) is synthesized by reacting ethylphenylmalonic acid diamide with formamide [5,6]. An alternative
method is the electrolytic reduction of phenobarbital or the catalytic reduction of the
appropriate 2-thiobarbituric acid .
- Veterinary Drugs and TreatmentsPrimidone is indicated for seizure control (idiopathic epilepsy, epileptiform convulsions) in the dog. Because it is rapidly converted into phenobarbital in this species (see Pharmacokinetics below), and has a greater incidence of hepatotoxicity and behavioral effects, most neurologists do not recommend its use. However, some clinicians feel that some animals not responding to phenobarbital do benefit from primidone therapy, perhaps as a result that PEMA has been demonstrated to potentiate the anticonvulsant activity of phenobarbital in animals. When compared with phenobarbital, increased incidence of hepatotoxicity associated with primidone is considered the major limitation to long-term therapy with this agent. Primidone is considered more toxic in rabbits and cats than in humans or dogs.
Primidone Preparation Products And Raw materials
- Raw materialsDiethyl 2-ethyl-2-phenylmalonate
Phenyl salicylate Hydroxyethyl starch PHENYL VALERATE Phenylacetone Silver sulfadiazine PHENYL RESIN 4-METHYLPRIMIDONE PHENOBARBITAL-D5 4-HYDROXYPHENOBARBITAL Phenobarbital dimethylphenobarbital PENTOBARBITAL-D5 ALPHENAL PHENOBARBITAL (2,4,5-13C3) DIHYDRO-5-PHENYL-5-PROPYL-4,6(1H,5H)-PYRIMIDINEDIONE 5-ETHYL-5-P-TOLYLBARBITURIC ACID 99+% 1,3-Bis(phenylmethyl)-5-ethyl-5-phenyl-2,4,6(1H,3H,5H)-pyrimidinetrion e MEPHOBARBITAL
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