Refractory seizure disorders

Also known as: Status epilepticus / Grand mal status

DrugDrug NameDrug Description
DB00829DiazepamA benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity. It is used in the treatment of severe anxiety disorders, as a hypnotic in the short-term management of insomnia, as a sedative and premedicant, as an anticonvulsant, and in the management of alcohol withdrawal syndrome. (From Martindale, The Extra Pharmacopoeia, 30th ed, p589) Given diazepam's storied history as a commonly used and effective medication for a variety of indications, contemporary advancements in the formulation and administration of the agent include the development and US FDA approval of an auto-injectable formulation for the rapid treatment of uncontrolled seizures in 2015-2016 [L5200]. Combining diazepam, a proven effective therapy for acute repetitive seizures, with an auto-injector designed for subcutaneous administration that is quickly and easily administered offers the potential for complete, consistent drug absorption and rapid onset of effect [L5200]. This current development is subsequently an important addition to the rescue therapy tool chest for patients with epilepsy [L5200].
DB00949FelbamateFelbamate is an anticonvulsant drug used in the treatment of epilepsy. In particular, in the adult patient population, it can be employed to treat partial seizures (with and without generalization). Alternatively, it is used to treat partial and generalized seizures associated with Lennox-Gastaut syndrome in children. It has a weak inhibitory effect on GABA receptor binding sites.
DB01320FosphenytoinFosphenytoin is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures. It works by slowing down impulses in the brain that cause seizures. Its main mechanism is to block frequency-dependent, use-dependent and voltage-dependent neuronal sodium channels, and therefore limit repetitive firing of action potentials.
DB06218LacosamideLacosamide is a functionalized amino acid that has activity in the maximal electroshock seizure test, and is indicated for the adjunctive treatment of partial-onset seizures and diabetic neuropathic pain. Recent studies indicate that Lacosamide only affects those neurons which are depolarized or active for long periods of time, typical of neurons at the focus of an epileptic seizure, as opposed to other antiepileptic drugs such as carbamazepine or lamotrigine which slow the recovery from inactivation and reduce the ability of neurons to fire action potentials.
DB01202LevetiracetamLevetiracetam is an anticonvulsant medication used to treat epilepsy. Levetiracetam may selectively prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity. Levetiracetam binds to the synaptic vesicle protein SV2A, which is thought to be involved in the regulation of vesicle exocytosis. Although the molecular significance of levetiracetam binding to synaptic vesicle protein SV2A is not understood, levetiracetam and related analogs showed a rank order of affinity for SV2A which correlated with the potency of their antiseizure activity in audiogenic seizure-prone mice.
DB00186LorazepamLorazepam is a short-acting and rapidly cleared benzodiazepine used commonly as a sedative and anxiolytic.[A957] It was developed by DJ Richards, presented and marketed initially by Wyeth Pharmaceuticals in the USA in 1977. The first historic FDA label approval is reported in 1985 by the company Mutual Pharm.[L5095]
DB00683MidazolamMidazolam is a short-acting hypnotic-sedative drug with anxiolytic, muscle relaxant, anticonvulsant, sedative, hypnotic, and amnesic properties.[A173842] It belongs to a class of drugs called _benzodiazepines_. This drug is unique from others in this class due to its rapid onset of effects and short duration of action.[A173842] Midazolam is available by oral, rectal, intranasal, intramuscular (IM), and intravenous (IV) routes and has been used in various biomedical applications, including dentistry, cardiac surgery, and endoscopic procedures as pre-anesthetic medication, and as an adjunct to local anesthesia.[F2977] This drug was initially approved by the US FDA in 1985, and has been approved for various indications since.[FDA label] In late 2018, the intramuscular preparation was approved by the FDA for the treatment of status epilepticus in adults.[FDA label] In May 2019, the nasal spray of midazolam was approved for the acute treatment of distinctive intermittent, stereotypic seizure episodes in patients 12 years of age and older. Midazolam is considered a schedule IV drug in the United States due to the low potential for abuse and low risk of dependence.[L5074]
DB00313Valproic AcidValproic acid, or valproate, is an fatty acid derivative and anticonvulsant originally synthesized in 1881 by Beverly S. Burton.[A178051] It enjoyed use as a popular organic solvent in industry and pharmaceutical manufacturing for nearly a century. In 1963, a serendipitous discovery was made by George Carraz during his investigations into the anticonvulsant effects of khelline when he found that all of his samples, dissolved in valproic acid, exerted a similar degree of anticonvulsive activity. It first received approval on February 28, 1978 from the FDA under the trade name Depakene.[L6190] Since then, it has been investigated for neuroprotective, anti-manic, and anti-migraine effects. It is currently a compound of interest in the field of oncology for its anti-proliferative effects and is the subject of many clinical trials in a variety of cancer types.
DrugDrug NameTargetType
DB00829DiazepamTranslocator proteintarget
DB00829DiazepamGamma-aminobutyric acid receptor subunit alpha-1target
DB00829DiazepamGamma-aminobutyric acid receptor subunit alpha-2target
DB00829DiazepamGamma-aminobutyric acid receptor subunit alpha-3target
DB00829DiazepamCytochrome P450 3A4enzyme
DB00829DiazepamSerum albumincarrier
DB00829DiazepamCytochrome P450 2C9enzyme
DB00829DiazepamCytochrome P450 2C19enzyme
DB00829DiazepamCytochrome P450 3A5enzyme
DB00829DiazepamCytochrome P450 3A7enzyme
DB00829DiazepamGamma-aminobutyric acid receptor subunit alpha-5target
DB00829DiazepamGamma-aminobutyric acid receptor subunit beta-1target
DB00829DiazepamGamma-aminobutyric acid receptor subunit beta-2target
DB00829DiazepamGamma-aminobutyric acid receptor subunit beta-3target
DB00829DiazepamGamma-aminobutyric acid receptor subunit gamma-1target
DB00829DiazepamGamma-aminobutyric acid receptor subunit gamma-2target
DB00829DiazepamGamma-aminobutyric acid receptor subunit gamma-3target
DB00829DiazepamGamma-aminobutyric acid receptor subunit deltatarget
DB00829DiazepamGamma-aminobutyric acid receptor subunit epsilontarget
DB00829DiazepamGamma-aminobutyric acid receptor subunit pitarget
DB00829DiazepamGamma-aminobutyric acid receptor subunit rho-1target
DB00829DiazepamGamma-aminobutyric acid receptor subunit rho-2target
DB00829DiazepamGamma-aminobutyric acid receptor subunit rho-3target
DB00829DiazepamGamma-aminobutyric acid receptor subunit thetatarget
DB00829DiazepamMultidrug resistance protein 1transporter
DB00829DiazepamCytochrome P450 2B6enzyme
DB00829DiazepamProstaglandin G/H synthase 1enzyme
DB00829DiazepamCytochrome P450 2C18enzyme
DB00829DiazepamCytochrome P450 2C8enzyme
DB00829DiazepamCytochrome P450 2E1enzyme
DB00829DiazepamGABA-A receptor (anion channel)target
DB00949FelbamateGlutamate receptor ionotropic, NMDA 3Atarget
DB00949FelbamateGlutamate receptor ionotropic, NMDA 2Btarget
DB00949FelbamateGlutamate receptor ionotropic, NMDA 2Atarget
DB00949FelbamateCytochrome P450 2C19enzyme
DB00949FelbamateCytochrome P450 3A4enzyme
DB00949FelbamateCytochrome P450 2E1enzyme
DB00949FelbamateCytochrome P450 2C9enzyme
DB01320FosphenytoinSodium channel protein type 5 subunit alphatarget
DB01320FosphenytoinCytochrome P450 2C19enzyme
DB01320FosphenytoinCytochrome P450 2B6enzyme
DB01320FosphenytoinCytochrome P450 2C9enzyme
DB01320FosphenytoinCytochrome P450 3A4enzyme
DB01320FosphenytoinSerum albumincarrier
DB01320FosphenytoinCytochrome P450 1A2enzyme
DB01320FosphenytoinUDP-glucuronosyltransferase 1-6enzyme
DB01320FosphenytoinUDP-glucuronosyltransferase 1-9enzyme
DB01320FosphenytoinCytochrome P450 2D6enzyme
DB01320FosphenytoinThyroxine-binding globulincarrier
DB06218LacosamideSodium channel protein type 9 subunit alphatarget
DB06218LacosamideSodium channel protein type 3 subunit alphatarget
DB06218LacosamideSodium channel protein type 10 subunit alphatarget
DB06218LacosamideCytochrome P450 2C19enzyme
DB06218LacosamideCytochrome P450 2C9enzyme
DB06218LacosamideCytochrome P450 3A4enzyme
DB01202LevetiracetamSynaptic vesicle glycoprotein 2Atarget
DB01202LevetiracetamMultidrug resistance protein 1transporter
DB01202LevetiracetamCanalicular multispecific organic anion transporter 1transporter
DB01202LevetiracetamVoltage-dependent N-type calcium channel subunit alpha-1Btarget
DB01202LevetiracetamCytochrome P450 3A4enzyme
DB00186LorazepamTranslocator proteintarget
DB00186LorazepamUDP-glucuronosyltransferase 2B15enzyme
DB00186LorazepamGABA-A receptor (anion channel)target
DB00186LorazepamCytochrome P450 3A4enzyme
DB00683MidazolamGamma-aminobutyric acid receptor subunit alpha-1target
DB00683MidazolamGamma-aminobutyric acid receptor subunit alpha-5target
DB00683MidazolamGamma-aminobutyric acid receptor subunit alpha-3target
DB00683MidazolamGamma-aminobutyric acid receptor subunit alpha-2target
DB00683MidazolamGamma-aminobutyric acid receptor subunit alpha-4target
DB00683MidazolamGamma-aminobutyric acid receptor subunit alpha-6target
DB00683MidazolamCytochrome P450 3A4enzyme
DB00683MidazolamCytochrome P450 3A5enzyme
DB00683MidazolamUDP-glucuronosyltransferase 1-4enzyme
DB00313Valproic AcidHistone deacetylase 9target
DB00313Valproic AcidShort/branched chain specific acyl-CoA dehydrogenase, mitochondrialtarget
DB00313Valproic AcidCytochrome P450 2A6enzyme
DB00313Valproic AcidCytochrome P450 2B6enzyme
DB00313Valproic AcidCytochrome P450 2C9enzyme
DB00313Valproic AcidSolute carrier family 22 member 5transporter
DB00313Valproic AcidSolute carrier family 22 member 6transporter
DB00313Valproic AcidSolute carrier family 22 member 8transporter
DB00313Valproic AcidMonocarboxylate transporter 1transporter
DB00313Valproic AcidSolute carrier family 22 member 7transporter
DB00313Valproic AcidCytochrome P450 3A5enzyme
DB00313Valproic AcidUDP-glucuronosyltransferase 1-9enzyme
DB00313Valproic AcidProstaglandin G/H synthase 1enzyme
DB00313Valproic AcidCytochrome P450 1A2enzyme
DB00313Valproic AcidCytochrome P450 2C18enzyme
DB00313Valproic AcidCytochrome P450 2C19enzyme
DB00313Valproic AcidCytochrome P450 2C8enzyme
DB00313Valproic AcidCytochrome P450 3A4enzyme
DB00313Valproic AcidUDP-glucuronosyltransferase 1-4enzyme
DB00313Valproic AcidUDP-glucuronosyltransferase 1-8enzyme
DB00313Valproic AcidUDP-glucuronosyltransferase 1-10enzyme
DB00313Valproic AcidUDP-glucuronosyltransferase 1-6enzyme
DB00313Valproic AcidUDP-glucuronosyltransferase 1-3enzyme
DB00313Valproic AcidUDP-glucuronosyltransferase 2B7enzyme
DB00313Valproic AcidUDP-glucuronosyltransferase 2B15enzyme
DB00313Valproic Acid2-oxoglutarate dehydrogenase, mitochondrialtarget
DB00313Valproic AcidSuccinate-semialdehyde dehydrogenase, mitochondrialtarget
DB00313Valproic AcidSodium channel proteintarget
DB00313Valproic AcidHistone deacetylase 2target
DB00313Valproic AcidPeroxisome proliferator-activated receptor alphatarget
DB00313Valproic AcidPeroxisome proliferator-activated receptor deltatarget
DB00313Valproic AcidPeroxisome proliferator-activated receptor gammatarget
DB00313Valproic AcidSerum albumincarrier
DB00313Valproic AcidUDP-glucuronosyltransferase 1-1enzyme
DB00313Valproic AcidSolute carrier organic anion transporter family member 2B1transporter
DrugDrug NamePhaseStatusCount
DB01202Levetiracetam2Unknown Status1
DB00829Diazepam2 / 3Completed1
DB00186Lorazepam2 / 3Completed1
DB01202LevetiracetamNot AvailableRecruiting1
DB00186LorazepamNot AvailableNot Yet Recruiting1
DB00186LorazepamNot AvailableRecruiting1
DB00683MidazolamNot AvailableRecruiting1
DB00818PropofolNot AvailableRecruiting1
DB00599ThiopentalNot AvailableRecruiting1
DB00313Valproic AcidNot AvailableRecruiting1
DB00313Valproic AcidNot AvailableUnknown Status1