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Phenytoin is an anticonvulsant agent and active metabolite of fosphenytoin.
Phenytoin is formed from fosphenytoin by tissue phosphatases.
Phenytoin inhibits neuronal voltage-gated sodium channels in a voltage-dependent manner.
CAS Number: 57-41-0
Molecular Formula: C15H12N2O2
Molecular Weight: 252.27
EINECS Number: 200-328-6
Synonyms: phenytoin; 5,5-DIPHENYLHYDANTOIN, 57-41-0; Diphenylhydantoin, 5,5-diphenylimidazolidine-2,4-dione, 4,5-Diphenyl-4-imidazoline-2-one, 5,5-Diphenyltetrahydroglyoxalin-4-one, 5,5-Diphenylhydantoin-2-13C, 3-15N, PHENYTOIN,USP, Dantoinal;Dantoinal klinos;Dantoinalklinos;Dantoine
Phenytoin reduces the neuronal firing frequency and decreases the amplitude of excitatory post-synaptic potentials (EPSPs) in electrically stimulated rat corticostriatal slices.
Phenytoin protects against seizures induced by maximal electroshock (MES) in mice (ED50 = 10 mg/kg).
Formulations containing phenytoin have been used in the treatment of tonic-clonic seizures and status epilepticus.
Phenytoin has a narrow therapeutic index and the relationship between dose and plasma.
Phenytoin concentration is non- linear: small dosage increases in some patients may produce large increases in plasma concentration with acute toxic adverse effects.
Similarly, a few missed doses or a small change in phenytoin absorption may result in a marked change in plasma phenytoin concentration.
Monitoring of plasma phenytoin concentration improves dosage adjustments.
The usual total plasma phenytoin concentration for optimum response is 0– 20 mg/ L (careful interpretation of total plasma phenytoin concentration is necessary in pregnancy, the elderly, and certain disease states where protein binding may be reduced and it may be more appropriate to measure free plasma phenytoin concentration).
Phenytoin has an overall favourable behavioural profile, although it has been occasionally associated with negative effects on mood and psychotic symptoms (especially at higher doses).
The cognitive profile is more problematic, especially in the attention and memory domains.
Cognitive adverse effects associated with phenytoin are often dose- dependent and may be particularly obvious in visually guided motor functions.
Phenytoin is a synthetic organic compound belonging to the hydantoin class of heterocyclic compounds and is one of the best-known anticonvulsant pharmaceuticals.
Phenytoin is widely recognized for its use in the management of certain types of seizures and is also known by the chemical name 5,5-diphenylhydantoin.
The molecular formula of Phenytoin is C₁₅H₁₂N₂O₂, and its molecular weight is approximately 252.27 g/mol.
Its CAS Registry Number is 57-41-0, which is commonly used for its identification in chemical, pharmaceutical, and regulatory databases.
The IUPAC name of Phenytoin is 5,5-diphenylimidazolidine-2,4-dione.
Phenytoin is also systematically described as 5,5-diphenyl-2,4-imidazolidinedione, reflecting the two carbonyl groups present within its hydantoin ring.
Phenytoin contains a five-membered imidazolidine ring with two nitrogen atoms and two carbonyl groups.
Two phenyl groups are attached to the same carbon atom at the 5-position of the hydantoin ring, giving the molecule its characteristic diphenyl-substituted structure.
Phenytoin is commonly known by several names and historical synonyms.
These include Diphenylhydantoin, 5,5-Diphenylhydantoin, DPH, Diphenine, Dilantin, Phenytoine, Fenitoin, Fenitoina, Hydantoin, and 5,5-Diphenyl-2,4-imidazolidinedione.
Phenytoin is structurally related to hydantoin, a five-membered cyclic urea derivative.
The addition of two phenyl groups at the 5-position substantially changes the physicochemical and biological properties of the parent hydantoin structure.
In its pure form, Phenytoin is described as a fine white or almost white crystalline powder.
Phenytoin is generally odorless or almost odorless and has been characterized as tasteless in toxicological chemical references.
Phenytoin has relatively low water solubility, which is an important characteristic of Phenytoin from a pharmaceutical formulation perspective.
The poor aqueous solubility has influenced the development of different pharmaceutical forms, including preparations based on phenytoin salts.
The chemical structure contains two nitrogen atoms and two oxygen atoms, with the oxygen atoms present as carbonyl groups.
The two phenyl rings provide a substantial hydrophobic portion of the molecule, while the hydantoin ring provides the principal heteroatom-containing functional framework.
Phenytoin is classified pharmacologically as an anticonvulsant or antiepileptic drug.
Its therapeutic activity is associated primarily with suppression of abnormal high-frequency neuronal electrical activity.
The precise molecular mechanism responsible for all of its therapeutic effects has not been completely established.
However, current pharmaceutical information indicates that Phenytoin is thought to act primarily through voltage-dependent blockade of neuronal sodium channels, reducing sustained high-frequency neuronal discharges.
This sodium-channel activity explains why Phenytoin can reduce the propagation of abnormal electrical activity within the nervous system.
Phenytoins pharmacological action therefore differs from simple sedative effects and is particularly relevant to the control of epileptic neuronal activity.
Phenytoin has a long history in the treatment of epilepsy and seizure disorders.
Its introduction represented an important development in anticonvulsant pharmacotherapy because it provided effective seizure control without being primarily used as a general anesthetic or sedative.
Phenytoin can be formulated as phenytoin itself or as pharmaceutical salts such as phenytoin sodium.
Phenytoin sodium has been developed partly to address formulation and solubility requirements associated with the poorly water-soluble parent compound.
Phenytoin is available in several pharmaceutical dosage forms, including oral tablets and capsules and certain injectable preparations.
Different formulations are selected according to the clinical circumstances and the required route of administration.
Phenytoin is also extensively studied in pharmaceutical chemistry because its pharmacokinetic behavior is unusual compared with many conventional drugs.
At therapeutic concentrations, its metabolism can become nonlinear, meaning that relatively small changes in exposure can produce disproportionately larger changes in blood concentration.
Phenytoin is metabolized primarily in the liver, with 5-(p-hydroxyphenyl)-5-phenylhydantoin, commonly abbreviated as HPPH, identified as its principal metabolite.
This metabolic pathway is relevant to both its pharmacological activity and the interpretation of its concentrations during clinical treatment.
Phenytoin has also been extensively investigated in relation to drug interactions.
Its metabolism and therapeutic concentration range mean that interactions with other medicines can be particularly important in pharmaceutical and clinical research.
From a chemical perspective, Phenytoin is therefore both a well-defined heterocyclic compound and an important pharmaceutical active ingredient.
Phenytoins combination of a diphenylhydantoin structure, low aqueous solubility, distinctive metabolism, and voltage-dependent sodium-channel activity has made it significant in medicinal chemistry and pharmacology.
NIST records extensive chemical information for Phenytoin, including its molecular formula, molecular weight, CAS number, structural information, mass spectrum, ultraviolet/visible spectrum, and gas-chromatographic data.
These analytical characteristics make Phenytoin suitable for identification and characterization in pharmaceutical and chemical laboratories.
Phenytoin is also historically associated with several pharmaceutical brand names, including Dilantin and Epanutin.
These names appear alongside numerous older synonyms in chemical reference databases because Phenytoin has been used medicinally for many decades.
Phenytoin is a synthetic 5,5-diphenylhydantoin compound with the formula C₁₅H₁₂N₂O₂ and CAS No. 57-41-0.
Its major significance comes from its established anticonvulsant activity, distinctive hydantoin structure, limited water solubility, hepatic metabolism, and extensive use in pharmaceutical research and medicine.
Melting point: 293-295 °C (lit.)
Boiling point: 395.45 °C (rough estimate)
Density: 1.1562 (rough estimate)
Bulk density: 400-450 kg/m3
Refractive index: 1.5906 (estimate)
Flash point: 11 °C
Storage temp.: 2-8 °C
Solubility: DMSO: soluble
pKa: pKa 8.43 (H2O, t = 25, I = 0.025) (Uncertain)
Form: Powder
Color: White to almost white
Biological source: Rabbit
Water solubility: <0.01 g/100 mL at 19 °C
Merck: 14,7322
BRN: 384532
Henry's Law Constant: 9.7 × 10⁵ mol/(m³Pa) at 25 °C, HSDB (2015)
Stability: Stable. Combustible. Incompatible with strong oxidizing agents, strong bases.
InChI: 1S/C15H12N2O2/c18-13-15(17-14(19)16-13,11-7-3-1-4-8-11)12-9-5-2-6-10-12/h1-10H,(H2,16,17,18,19)
InChIKey: CXOFVDLJLONNDW-UHFFFAOYSA-N
SMILES: O=C1NC(=O)C(N1)(c2ccccc2)c3ccccc3
Phenytoin is a first- generation antiepileptic drug (AED) known with the proprietary brand name of Epanutin (Pfizer, Tadworth) in the UK and Dilantin (Pfizer, New York, NY) in the USA.
Phenytoin advice to minimize risk when switching patients with epilepsy between different manufacturers’ products (incl. generic products): Doctors are advised to ensure that their patients are maintained on a specific manufacturer’s product.
Phenytoin is a 5,5-diphenyl-substituted hydantoin in which two phenyl groups are attached to the same carbon atom of the imidazolidine-2,4-dione ring.
This structural arrangement gives the molecule a relatively hydrophobic character and contributes to its limited solubility in water.
Phenytoin has the molecular formula C₁₅H₁₂N₂O₂ and a molecular weight of 252.268 g/mol.
Phenytoin s CAS Registry Number is 57-41-0, while its PubChem Compound ID is 1775.
Phenytoin contains a five-membered heterocyclic ring with two nitrogen atoms and two carbonyl groups.
The two carbonyl functionalities are characteristic of the hydantoin framework and contribute to Phenytoin's hydrogen-bonding and acid-base properties.
Phenytoin is also known as 5,5-diphenylhydantoin, Diphenylhydantoin, DPH, 5,5-diphenylimidazolidine-2,4-dione, and 5,5-diphenyl-2,4-imidazolidinedione.
Numerous historical pharmaceutical names, including Dilantin, Epanutin, Diphenine, and Diphantoin, are also associated with phenytoin.
Pure phenytoin is generally described as a fine white or almost white crystalline powder.
Phenytoin is essentially odorless or almost odorless and has been characterized in chemical reference literature as tasteless.
The physicochemical properties of phenytoin are important because the free compound has poor aqueous solubility.
This characteristic has influenced the development of alternative formulations, particularly phenytoin sodium, which is used when greater aqueous solubility is required.
Phenytoin behaves as a weakly acidic compound because of the imide hydrogens associated with the hydantoin ring.
This property permits formation of salts such as phenytoin sodium and is important when considering pharmaceutical formulation and dissolution behavior.
The limited water solubility of phenytoin can influence its absorption and distribution after administration.
Phenytoin also explains why different pharmaceutical formulations can exhibit substantially different dissolution and absorption characteristics.
Phenytoin is primarily recognized for its anticonvulsant activity.
Its pharmacological effect is thought to involve voltage-dependent blockade of neuronal sodium channels, which reduces sustained high-frequency neuronal discharges.
Unlike compounds that suppress neuronal activity primarily through generalized sedation, phenytoin acts particularly on the electrical activity associated with repetitive neuronal firing.
This mechanism is one of the principal reasons for its long-standing role in the treatment of specific seizure disorders.
Phenytoin is extensively metabolized in the liver after administration.
Phenytoin s metabolism produces 5-(p-hydroxyphenyl)-5-phenylhydantoin, commonly referred to as HPPH, which is identified as its principal metabolite in pharmaceutical references.
The metabolism of phenytoin is particularly important because Phenytoin demonstrates capacity-limited or nonlinear pharmacokinetics over clinically relevant concentration ranges.
As metabolic enzymes become increasingly saturated, relatively small increases in dose can produce disproportionately large increases in circulating drug concentrations.
This nonlinear behavior makes phenytoin an important compound in pharmacokinetic research.
Phenytoin has been extensively investigated in studies involving dose optimization, drug interactions, enzyme activity, metabolism, and therapeutic drug monitoring.
Phenytoin is also an important compound in analytical and pharmaceutical research laboratories.
Its well-characterized molecular structure, established reference standards, and extensive pharmacokinetic literature make it useful for method development, identification, impurity analysis, and pharmaceutical quality-control studies.
Analytical laboratories can characterize phenytoin using techniques such as high-performance liquid chromatography, liquid chromatography–mass spectrometry, gas chromatography after suitable preparation, UV-visible spectroscopy, and mass spectrometry.
NIST provides reference information for phenytoin including mass spectral, UV/visible, and chromatographic data.
Phenytoin is also used as a reference substance in investigations of pharmaceutical metabolism.
Phenytoin s metabolic pathways have been studied to understand hepatic enzyme activity and the influence of other substances on drug biotransformation.
Phenytoin's pharmacokinetic behavior has made it particularly valuable for research into drug-drug interactions.
Changes in hepatic enzyme activity can alter phenytoin concentrations, while phenytoin itself can influence the metabolism of other pharmaceutical compounds.
Phenytoin is commercially encountered both as the free compound and in pharmaceutical forms based on its sodium salt.
The distinction is important because phenytoin and phenytoin sodium do not have identical physicochemical behavior, particularly with respect to aqueous solubility and formulation.
Different dosage forms include oral tablets, chewable tablets, oral suspensions, and injectable preparations.
Current pharmaceutical labeling describes phenytoin formulations with different absorption characteristics and emphasizes the importance of maintaining appropriate therapeutic concentrations.
Phenytoin is also significant from a pharmaceutical development perspective because formulation composition can affect its dissolution and bioavailability.
Poor aqueous solubility is therefore an important consideration when developing new phenytoin formulations, analytical methods, or alternative delivery systems.
Phenytoin's extensive historical use has generated a large body of information concerning its chemical behavior, pharmacology, metabolism, and analytical characteristics.
Consequently, it remains an important reference compound in pharmaceutical sciences even though newer anticonvulsant agents are also widely available.
Phenytoin is a well-characterized diphenylhydantoin derivative combining a distinctive heterocyclic structure with important pharmaceutical properties.
Phenytoin low aqueous solubility, hepatic metabolism, nonlinear pharmacokinetics, and established anticonvulsant activity make it relevant to pharmaceutical manufacturing, analytical chemistry, medicinal chemistry, and biomedical research.
Uses:
Reduces incidence of grand mal seizures; appears to stabilize excitable membranes perhaps through effects on Na+, K+, and Ca2+ channels.
Phenytoin has the same main effects on the heart as lidocaine.
Its use is essentially limited, and it is primarily used only as an oral replacement of lidocaine for paroxysmal tachycardia that is caused particularly by intoxication of digitalis drugs.
Phenytoin has been used for phenytoin treatment.
Phenytoin has also been used to slow down or prevent mesoendoderm cell migration.
Phenytoin is one of very few drugs that displays zero-order (or saturation) kinetics in its metabolism.At low blood levels the rate of phenytoin metabolism is proportional to the drug’s blood 1evels (i.e., first-order kinetics).
However, at the higher blood levels usually required to control seizures, the maximum capacity of drug-metabolizing enzymes is often exceeded (i.e., the enzyme is saturated), and further increases in the dose of phenytoin may lead to a disproportionate increase in the drug’s blood concentration.
Since the plasma levels continue to increase in such a situation, steady-state levels are not attained, and toxicity may ensue.
Calculation of half-life (t1/2) values for phenytoin often is meaningless, since the apparent half-life varies with the drug blood level.
Phenytoin is primarily used as an antiepileptic and anticonvulsant pharmaceutical compound for the control of seizures.
Phenytoin has a long history of clinical use and remains an established treatment option for several types of epileptic disorders.
Oral phenytoin preparations are used for the management of generalized tonic-clonic seizures.
These formulations are intended to reduce abnormal electrical activity in the brain and help prevent recurrent seizure episodes.
Phenytoin is also used in the treatment of complex partial seizures, which are also described in pharmaceutical labeling as psychomotor or temporal-lobe seizures.
Its ability to reduce repetitive neuronal firing makes it useful for controlling these seizure types.
Another important application is the prevention and treatment of seizures associated with neurosurgery.
Phenytoin may be used when seizure control is required during or following certain neurosurgical procedures.
Parenteral phenytoin sodium has a specific role in the treatment of generalized tonic-clonic status epilepticus.
Because intravenous administration can rapidly provide systemic drug exposure, it may be used when urgent seizure management is required and oral administration is not possible.
Intravenous phenytoin sodium can also be used as a short-term substitute for oral phenytoin when oral administration cannot be achieved.
This application provides clinicians with an alternative route while maintaining anticonvulsant therapy.
Phenytoin is available in several pharmaceutical dosage forms, including tablets, chewable tablets, capsules, and injectable formulations.
The availability of different forms allows Phenytoin to be incorporated into treatment strategies according to the patient's clinical circumstances and route-of-administration requirements.
Phenytoin is also important in pharmaceutical formulation research.
Its relatively low aqueous solubility has encouraged research into salts, alternative formulations, dissolution enhancement, and drug-delivery approaches designed to improve pharmaceutical performance.
Phenytoin is widely used in pharmacokinetic research because its concentration-dependent metabolism produces nonlinear pharmacokinetic behavior.
This makes phenytoin a useful model compound for investigating dose-concentration relationships, drug metabolism, and therapeutic drug monitoring.
Phenytoin is commonly investigated in therapeutic drug monitoring studies because maintaining appropriate circulating concentrations is important for balancing seizure control against concentration-related adverse effects.
Measurement of serum phenytoin concentrations can assist with dosage adjustment in appropriate clinical situations.
Another important research application involves drug-drug interaction studies.
Phenytoin has clinically significant interactions with numerous medicines, making it a valuable compound for studying hepatic enzyme induction, metabolic interactions, and changes in drug exposure.
Phenytoin is also used as an analytical target in pharmaceutical quality-control laboratories.
Analytical methods can be developed to identify and quantify phenytoin in pharmaceutical products, biological samples, dissolution media, and formulation-development studies.
In pharmaceutical analysis, phenytoin can be investigated using techniques such as high-performance liquid chromatography, liquid chromatography–mass spectrometry, UV-visible spectroscopy, and mass spectrometry.
These applications support identity testing, assay determination, impurity evaluation, pharmacokinetic analysis, and formulation research.
Phenytoin is additionally used in medicinal chemistry and pharmaceutical research as a representative hydantoin-based anticonvulsant.
Its structure provides a useful basis for investigating relationships between molecular structure, ionization, lipophilicity, pharmacological activity, and anticonvulsant properties.
Phenytoin and related hydantoin compounds have also been examined in research involving structure-activity relationships.
Such studies can help researchers understand how modifications to the hydantoin ring or aromatic substituents influence biological activity and physicochemical properties.
Phenytoin has applications in biomedical and pharmacological research focused on neuronal excitability and voltage-dependent sodium channels.
Its established mechanism of reducing sustained high-frequency neuronal firing makes it a useful reference compound in studies of neuronal ion-channel pharmacology.
Phenytoin is also relevant to metabolism and biotransformation research because it undergoes extensive hepatic metabolism and produces identifiable metabolites such as 5-(p-hydroxyphenyl)-5-phenylhydantoin.
These characteristics make it useful for studying metabolic pathways and enzyme-mediated drug transformation.
In toxicological and clinical laboratory research, phenytoin can be investigated as a model compound for concentration-dependent toxicity and therapeutic-window assessment.
Such work can involve the relationship between circulating drug concentrations, protein binding, metabolism, and pharmacological or adverse effects.
Phenytoin sodium and related injectable formulations are also relevant to emergency pharmaceutical practice because parenteral therapy can be used when rapid anticonvulsant treatment is required in specific clinical circumstances.
However, intravenous phenytoin requires careful administration and monitoring because rapid administration can produce serious cardiovascular reactions.
Phenytoin extend beyond its traditional role as an anticonvulsant and include pharmaceutical formulation, analytical chemistry, pharmacokinetic research, therapeutic drug monitoring, medicinal chemistry, metabolism studies, toxicology, and neurological research.
Its combination of established clinical activity, distinctive hydantoin chemistry, limited aqueous solubility, and well-characterized pharmacokinetics makes phenytoin an important compound in both pharmaceutical applications and scientific research.
Safety Profile:
Confirmed carcinogen producing lymphoma, Hodgkin's disease, tumors of the skin and appendages.
Experimental carcinogenic and tumorigenic data.
A human poison by ingestion.
Poison experimentally by ingestion, subcutaneous, intravenous, and intraperitoneal routes.
Moderately toxic by an unspecified route.
Experimental teratogenic and reproductive effects.
Human systemic effects by ingestion: dermatitis, change in motor activity (specific assay), ataxia (loss of muscle coordmation), degenerative brain changes, encephalitis, hallucinations, dtstorted perceptions, irritabihty, and jaundice.
Phenytoin should be handled as a pharmacologically active chemical and should not be treated as an ordinary laboratory powder.
Safety information indicates potential hazards associated with ingestion, inhalation, skin exposure, and prolonged exposure, so appropriate laboratory controls are important when handling the substance.
Exposure to phenytoin can produce effects on the central nervous system, particularly when systemic concentrations become excessive.
Reported toxic effects can include nystagmus, ataxia, slurred speech, nausea, vomiting, lethargy, confusion, and, in severe poisoning, coma.
The severity of phenytoin toxicity is strongly related to the amount of drug absorbed and the resulting concentration in the body.
Because phenytoin exhibits nonlinear pharmacokinetics, relatively small increases in exposure can sometimes produce disproportionately large increases in circulating concentrations.
Phenytoin can cause neurological adverse effects even at therapeutic doses in susceptible individuals.
Dizziness, impaired coordination, abnormal eye movements, and changes in mental alertness are among the effects associated with excessive or poorly tolerated exposure.
Long-term exposure to phenytoin in therapeutic use can also produce characteristic adverse effects.
These may include gingival enlargement, peripheral neuropathy, changes in coordination, and other neurological or connective-tissue effects depending on treatment duration and individual susceptibility.
Phenytoin can cause serious hypersensitivity reactions in some individuals.
Skin reactions can range from relatively mild rashes to rare but potentially life-threatening conditions such as Stevens–Johnson syndrome and toxic epidermal necrolysis.
Supply Of Phenytoin:
For further information about Phenytoin, including available product grades, technical specifications, application suitability and supply options, please contact Ataman Kimya.
