Huntington's Disease (HD)

Also known as: Huntington's chorea / Huntington disease / Huntington's disease

DrugDrug NameDrug Description
DB00915AmantadineAn antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake.
DB12161DeutetrabenazineDeutetrabenazine is a novel, highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor indicated for the management of chorea associated with Huntington’s disease. It is a hexahydro-dimethoxybenzoquinolizine derivative and a deuterated [DB04844] [A32046]. The presence of deuterium in deutetrabenazine increases the half-lives of the active metabolite and prolongs their pharmacological activity by attenuating CYP2D6 metabolism of the compound [A32046]. This allows less frequent dosing and a lower daily dose with improvement in tolerability [A32043]. Decreased plasma fluctuations of deutetrabenazine due to attenuated metabolism may explain a lower incidence of adverse reactions associated with deutetrabenazine [A32042]. Deutetrabenazine is a racemic mixture containing RR-Deutetrabenazine and SS-Deutetrabenazine [FDA Label]. Huntington's disease (HD) is a hereditary, progressive neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and neuropsychiatric disturbances [A32043] that interfere with daily functioning and significantly reduce the quality of life. The most prominent physical symptom of HD that may increase the risk of injury is chorea, which is an involuntary, sudden movement that can affect any muscle and flow randomly across body regions [A32046]. Psychomotor symptoms of HD, such as chorea, are related to hyperactive dopaminergic neurotransmission [A14081]. Deutetrabenazine depletes the levels of presynaptic dopamine by blocking VMAT2, which is responsible for the uptake of dopamine into synaptic vesicles in monoaminergic neurons and exocytotic release [A14081]. As with other agents for the treatment of neurodegenerative diseases, deutetrabenazine is a drug to alleviate the motor symptoms of HD and is not proposed to halt the progression of the disease [T28]. In clinical trials of patients with HD, 12 weeks of treatment of deutetrabenazine resulted in overall improvement in mean total maximal chorea scores and motor signs than placebo [A32046]. It was approved by FDA in April 2017 and is marketed under the trade name Austedo as oral tablets.
DB00623FluphenazineA phenothiazine used in the treatment of psychoses. Its properties and uses are generally similar to those of chlorpromazine.
DB00502HaloperidolHaloperidol is a high potency first-generation (typical) antipsychotic and one of the most frequently used antipsychotic medications used worldwide.[A180616] While haloperidol has demonstrated pharmacologic activity at a number of receptors in the brain,[A27477] it exerts its antipsychotic effect through its strong antagonism of the dopamine receptor (mainly D2), particularly within the mesolimbic and mesocortical systems of the brain. Haloperidol is indicated for the treatment of the manifestations of several psychotic disorders including schizophrenia, acute psychosis, Tourette syndrome, and other severe behavioural states.[F4645] It is also used off-label for the management of chorea associated with Huntington's disease and for the treatment of intractable hiccups as it is a potent antiemetic. Dopamine-antagonizing medications such as haloperidol are though to improve psychotic symptoms and states that are caused by an over-production of dopamine, such as schizophrenia, which is theorized to be caused by a hyperdopaminergic state within the limbic system of the brain.[A34360] Use of the first-generation antipsychotics (including haloperidol) is considered highly effective for the management of the "positive" symptoms of schizophrenia including hallucinations, hearing voices, aggression/hostility, disorganized speech, and psychomotor agitation. However, this class of drugs is also limited by the development of movement disorders induced by dopamine-blockade such as drug-induced parkinsonism, akathisia, dystonia, tardive dyskinesia, as well as other side effects including sedation, weight gain, and prolactin changes. While there are limited high-quality studies comparing haloperidol to lower-potency first-generation antipsychotics such as [DB00477], [DB01624], [DB00623], and [DB01403], haloperidol typically demonstrates the least amount of side effects within this class, but demonstrates a stronger disposition for causing extrapyramidal symptoms (EPS).[A180613, A180616, A180625] These other low‐potency antipsychotics are limited by their lower affinity for dopamine receptors, which requires a higher dose to effectively treat symptoms of schizophrenia. In addition, they block many receptors other than the primary target (dopamine receptors), such as cholinergic or histaminergic receptors, resulting in a higher incidence of side effects such as sedation, weight gain, and hypotension. Interestingly, in vivo pharmacogenetic studies have demonstrated that the metabolism of haloperidol may be modulated by genetically determined polymorphic _CYP2D6_ activity. However, these findings contradict the findings from studies in vitro with human liver microsomes and from drug interaction studies in vivo. Inter-ethnic and pharmacogenetic differences in haloperidol metabolism may possibly explain these observations.[A32346] First-generation antipsychotic drugs have largely been replaced with second- and third-generation (atypical) antipsychotics such as [DB00734], [DB00334], [DB00363], [DB01224], [DB01238], and [DB00246]. However, haloperidol use remains widespread and is considered the benchmark for comparison in trials of the newer generation antipsychotics.[A180625] The efficacy of haloperidol was first established in controlled trials in the 1960s.[A180610]
DB04844TetrabenazineA drug formerly used as an antipsychotic but now used primarily in the symptomatic treatment of various hyperkinetic disorders. It is a monoamine depletor and used as symptomatic treatment of chorea associated with Huntington's disease. FDA approved on August 15, 2008.
DrugDrug NameTargetType
DB00915AmantadineDopamine D2 receptortarget
DB00915AmantadineMatrix protein 2target
DB00915AmantadineAromatic-L-amino-acid decarboxylaseenzyme
DB00915AmantadineAmine oxidase [flavin-containing] Benzyme
DB00915AmantadineSolute carrier family 22 member 2transporter
DB00915AmantadineSolute carrier family 22 member 1transporter
DB00915AmantadineGlutamate receptor ionotropic, NMDA 3Atarget
DB00915AmantadineNeuronal acetylcholine receptor subunit alpha-7target
DB00915AmantadineNeuronal acetylcholine receptor subunit alpha-4target
DB00915AmantadineNeuronal acetylcholine receptor subunit alpha-3target
DB12161DeutetrabenazineSynaptic vesicular amine transportertarget
DB12161DeutetrabenazineCarbonyl reductase [NADPH] 1enzyme
DB12161DeutetrabenazineCarbonyl reductase [NADPH] 3enzyme
DB12161DeutetrabenazineCytochrome P450 2D6enzyme
DB12161DeutetrabenazineCytochrome P450 1A2enzyme
DB12161DeutetrabenazineCytochrome P450 3A5enzyme
DB12161DeutetrabenazineCytochrome P450 3A4enzyme
DB00623FluphenazineDopamine D2 receptortarget
DB00623FluphenazineDopamine D1 receptortarget
DB00623FluphenazineCytochrome P450 2D6enzyme
DB00623FluphenazineMultidrug resistance protein 1transporter
DB00623FluphenazineCytochrome P450 2E1enzyme
DB00623FluphenazineAndrogen receptortarget
DB00623Fluphenazine5-hydroxytryptamine receptor 2Atarget
DB00623Fluphenazine5-hydroxytryptamine receptor 2Ctarget
DB00502HaloperidolDopamine D2 receptortarget
DB00502HaloperidolGlutamate receptor ionotropic, NMDA 2Btarget
DB00502HaloperidolDopamine D1 receptortarget
DB00502HaloperidolCytochrome P450 1A2enzyme
DB00502HaloperidolCytochrome P450 2D6enzyme
DB00502Haloperidol5-hydroxytryptamine receptor 2Atarget
DB00502HaloperidolDopamine D3 receptortarget
DB00502HaloperidolCytochrome P450 3A4enzyme
DB00502HaloperidolCytochrome P450 3A5enzyme
DB00502HaloperidolCytochrome P450 3A7enzyme
DB00502HaloperidolMultidrug resistance protein 1transporter
DB00502HaloperidolCarbonyl reductase [NADPH] 1enzyme
DB00502HaloperidolUDP-glucuronosyltransferase 1-9enzyme
DB00502HaloperidolCytochrome P450 2C19enzyme
DB00502HaloperidolCytochrome P450 2C9enzyme
DB00502HaloperidolMelanin-concentrating hormone receptor 1target
DB00502HaloperidolSynaptic vesicular amine transportertarget
DB00502Haloperidol5-hydroxytryptamine receptor 2Ctarget
DB00502HaloperidolSigma non-opioid intracellular receptor 1target
DB00502HaloperidolHistamine H1 receptortarget
DB00502HaloperidolMuscarinic acetylcholine receptor M3target
DB00502HaloperidolAlpha-1A adrenergic receptortarget
DB00502HaloperidolAlpha-2A adrenergic receptortarget
DB00502HaloperidolAlpha-2B adrenergic receptortarget
DB00502HaloperidolAlpha-2C adrenergic receptortarget
DB00502Haloperidol5-hydroxytryptamine receptor 1Atarget
DB00502Haloperidol5-hydroxytryptamine receptor 6target
DB00502Haloperidol5-hydroxytryptamine receptor 7target
DB00502HaloperidolCytochrome P450 1A1enzyme
DB04844TetrabenazineSynaptic vesicular amine transportertarget
DB04844TetrabenazineCytochrome P450 2D6enzyme
DB04844TetrabenazineDopamine D2 receptortarget
DB04844TetrabenazineCarbonyl reductase [NADPH] 1enzyme
DrugDrug NamePhaseStatusCount
DB13134Fluorine F-181Completed1
DB01586Ursodeoxycholic acid1Unknown Status1
DB00148Creatine1 / 2Completed1
DB11725Latrepirdine1 / 2Completed1
DB01017Minocycline1 / 2Completed1
DB01039Fenofibrate2Active Not Recruiting1
DB01356Lithium cation2Completed1
DB15155Pepinemab2Active Not Recruiting1
DB06819Phenylbutyric acid2Completed1
DB00313Valproic acid2Completed1
DB01017Minocycline2 / 3Completed1
DB11947Pridopidine2 / 3Completed1
DB09341Dextrose, unspecified form3Terminated1
DB08887Icosapent ethyl3Completed1
DB01043Memantine4Unknown Status1
DB00980RamelteonNot AvailableWithdrawn1