Troriluzole

Last updated
Troriluzole
Troriluzole.svg
Clinical data
Other namesTrigriluzole, BHV-4157, FC-4157
Routes of
administration
By mouth
Identifiers
  • 2-amino-N-[2-[methyl-[2-oxo-2-[[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino]ethyl]amino]-2-oxoethyl]acetamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C15H16F3N5O4S
Molar mass 419.38 g·mol−1
3D model (JSmol)
  • CN(CC(=O)NC1=NC2=C(S1)C=C(C=C2)OC(F)(F)F)C(=O)CNC(=O)CN
  • InChI=1S/C15H16F3N5O4S/c1-23(13(26)6-20-11(24)5-19)7-12(25)22-14-21-9-3-2-8(4-10(9)28-14)27-15(16,17)18/h2-4H,5-7,19H2,1H3,(H,20,24)(H,21,22,25)
  • Key:YBZSGIWIPOUSHY-UHFFFAOYSA-N

Troriluzole (trigriluzole) is an experimental medication that has been investigated as a potential treatment for spinocerebellar ataxia type 3 (SCA3), [1] [2] [3] [4] obsessive-compulsive disorder, [3] [4] and glioblastoma. [5] It is a prodrug formulation of the medication riluzole. [3] [5]

Contents

Pharmacology

Pharmacokinetics

While riluzole is typically taken twice-daily and on an empty stomach, troriluzole may offer a potential once-daily dosing with or without food along with greater bioavailability. [3] [5]

Research

In 2024, researchers published a study in the Journal of Neurochemistry that reported troriluzole could reverse some early Alzheimer's disease brain changes in mice, reduce harmful glutamate levels, and improve memory and learning abilities. [6] [7]

Related Research Articles

Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements, that indicates dysfunction of parts of the nervous system that coordinate movement, such as the cerebellum.

<span class="mw-page-title-main">Sertraline</span> Antidepressant (SSRI class) medication

Sertraline, sold under the brand name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. The effectiveness of sertraline for depression is similar to that of other antidepressants, and the differences are mostly confined to side effects. Sertraline is better tolerated than the older tricyclic antidepressants. Sertraline is effective for panic disorder, social anxiety disorder, generalized anxiety disorder (GAD), and obsessive–compulsive disorder (OCD). Although approved for post-traumatic stress disorder (PTSD), sertraline leads to only modest improvement in this condition. Sertraline also alleviates the symptoms of premenstrual dysphoric disorder (PMDD) and can be used in sub-therapeutic doses or intermittently for its treatment.

<span class="mw-page-title-main">Minocycline</span> Antibiotic medication

Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as some occurring in certain forms of pneumonia. It is generally less preferred than the tetracycline doxycycline. Minocycline is also used for the treatment of acne and rheumatoid arthritis. It is taken by mouth or applied to the skin.

<span class="mw-page-title-main">Aripiprazole</span> Atypical antipsychotic

Aripiprazole, sold under the brand names Abilify and Aristada, among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder; other uses include as an add-on treatment in major depressive disorder and obsessive–compulsive disorder (OCD), tic disorders, and irritability associated with autism. Aripiprazole is taken by mouth or via injection into a muscle. A Cochrane review found low-quality evidence of effectiveness in treating schizophrenia.

<span class="mw-page-title-main">Riluzole</span> Medication used to treat amyotrophic lateral sclerosis

Riluzole is a medication used to treat amyotrophic lateral sclerosis and other motor neuron diseases. Riluzole delays the onset of ventilator-dependence or tracheostomy in some people and may increase survival by two to three months. Riluzole is available in tablet and liquid form.

<span class="mw-page-title-main">Memantine</span> Medication used to treat Alzheimers disease

Memantine, sold under the brand name Axura among others, is a medication used to slow the progression of moderate-to-severe Alzheimer's disease. It is taken by mouth.

<span class="mw-page-title-main">Friedreich's ataxia</span> Rare autosomal-recessive human disease


Friedreich's ataxia (FRDA) is a rare, inherited, autosomal recessive neurodegenerative disorder that primarily affects the nervous system, causing progressive damage to the spinal cord, peripheral nerves, and cerebellum, leading to impaired muscle coordination (ataxia). The condition typically manifests in childhood or adolescence, with initial symptoms including difficulty walking, loss of balance, and poor coordination. As the disease progresses, it can also impact speech, vision, and hearing. Many individuals with Friedreich's ataxia develop scoliosis, diabetes, and hypertrophic cardiomyopathy, a serious heart condition that is a leading cause of mortality in patients.

<span class="mw-page-title-main">Clomipramine</span> Antidepressant

Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used in the treatment of various conditions, most notably obsessive–compulsive disorder but also many other disorders, including hyperacusis, panic disorder, major depressive disorder, trichotillomania, body dysmorphic disorder and chronic pain. It has also been notably used to treat premature ejaculation and the cataplexy associated with narcolepsy.

<span class="mw-page-title-main">Spinocerebellar ataxia</span> Medical condition

Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of spinocerebellar ataxia at any given time. SCA is hereditary, progressive, degenerative, and often fatal. There is no known effective treatment or cure. SCA can affect anyone of any age. The disease is caused by either a recessive or dominant gene. In many cases people are not aware that they carry a relevant gene until they have children who begin to show signs of having the disorder. Currently, research is being conducted at Universities, such as the University of Minnesota, to elucidate many of the unknown characteristics of the disease.

<span class="mw-page-title-main">Quinpirole</span> Chemical compound

Quinpirole is a psychoactive drug and research chemical which acts as a selective D2 and D3 receptor agonist. It is used in scientific research. Quinpirole has been shown to increase locomotion and sniffing behavior in mice treated with it. At least one study has found that quinpirole induces compulsive behavior symptomatic of obsessive compulsive disorder in rats. Another study in rats show that quinpirole produces significant THC-like effects when metabolic degradation of anandamide is inhibited, supporting the hypothesis that these effects of quinpirole are mediated by cannabinoid CB1 receptors. Quinpirole may also reduce relapse in adolescent rat models of cocaine addiction.

<span class="mw-page-title-main">Pramipexole</span> Dopamine agonist medication

Pramipexole, sold under the brand Mirapex among others, is a medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In Parkinson's disease it may be used alone or together with levodopa. It is taken by mouth. Pramipexole is a dopamine agonist of the non-ergoline class.

<span class="mw-page-title-main">Ataxin 1</span> Protein-coding gene in the species Homo sapiens

Ataxin-1 is a DNA-binding protein which in humans is encoded by the ATXN1 gene.

<span class="mw-page-title-main">FOSB</span> Protein

Protein fosB, also known as FosB and G0/G1 switch regulatory protein 3 (G0S3), is a protein that in humans is encoded by the FBJ murine osteosarcoma viral oncogene homolog B (FOSB) gene.

<span class="mw-page-title-main">GTS-21</span> Chemical compound

GTS-21 is a drug that has been shown to enhance memory and cognitive function. It has been studied for its potential therapeutic uses, particularly in the treatment of neurodegenerative diseases and psychiatric disorders.

<span class="mw-page-title-main">Obsessive–compulsive disorder</span> Mental and behavioral disorder

Obsessive–compulsive disorder (OCD) is a mental and behavioral disorder in which an individual has intrusive thoughts and feels the need to perform certain routines (compulsions) repeatedly to relieve the distress caused by the obsession, to the extent where it impairs general function.

<span class="mw-page-title-main">Opioid overdose</span> Toxicity due to excessive consumption of opioids

An opioid overdose is toxicity due to excessive consumption of opioids, such as morphine, codeine, heroin, fentanyl, tramadol, and methadone. This preventable pathology can be fatal if it leads to respiratory depression, a lethal condition that can cause hypoxia from slow and shallow breathing. Other symptoms include small pupils and unconsciousness; however, its onset can depend on the method of ingestion, the dosage and individual risk factors. Although there were over 110,000 deaths in 2017 due to opioids, individuals who survived also faced adverse complications, including permanent brain damage.

The biology of obsessive–compulsive disorder (OCD) refers to biologically based theories about the mechanism of OCD. Cognitive models generally fall into the category of executive dysfunction or modulatory control. Neuroanatomically, functional and structural neuroimaging studies implicate the prefrontal cortex (PFC), basal ganglia (BG), insula, and posterior cingulate cortex (PCC). Genetic and neurochemical studies implicate glutamate and monoamine neurotransmitters, especially serotonin and dopamine.

<span class="mw-page-title-main">Mavoglurant</span> Chemical compound

Mavoglurant (developmental code name AFQ-056) is an experimental drug candidate for the treatment of fragile X syndrome and other conditions. It exerts its effect as an antagonist of the metabotropic glutamate receptor 5 (mGluR5).

<span class="mw-page-title-main">Spinocerebellar ataxia type 1</span> Rare neurodegenerative disorder

Spinocerebellar ataxia type 1 (SCA1) is a rare autosomal dominant disorder, which, like other spinocerebellar ataxias, is characterized by neurological symptoms including dysarthria, hypermetric saccades, and ataxia of gait and stance. This cerebellar dysfunction is progressive and permanent. First onset of symptoms is normally between 30 and 40 years of age, though juvenile onset can occur. Death typically occurs within 10 to 30 years from onset.

References

  1. Meglio, Marco (25 June 2023). "Biohaven Submits New Drug Application for Troriluzole as Spinocerebellar Ataxia Type 3 Therapy". NeurologyLive. Retrieved 17 February 2024.
  2. Waldron, James (27 July 2023). "Further blow for Biohaven as FDA refuses to consider failed rare disease drug for approval". Fierce Biotech. Retrieved 17 February 2024.
  3. 1 2 3 4 Grassi G, Cecchelli C, Vignozzi L, Pacini S (2020). "Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder". Journal of Experimental Pharmacology . 12: 695–706. doi: 10.2147/JEP.S255375 . PMC   7801912 . PMID   33447096.
  4. 1 2 van Roessel PJ, Grassi G, Aboujaoude EN, Menchón JM, Van Ameringen M, Rodríguez CI (January 2023). "Treatment-resistant OCD: Pharmacotherapies in adults". Comprehensive Psychiatry. 120: 152352. doi:10.1016/j.comppsych.2022.152352. hdl: 2445/192315 . PMID   36368186.
  5. 1 2 3 Silk AW, Saraiya B, Groisberg R, Chan N, Spencer K, Girda E, Shih W, Palmeri M, Saunders T, Berman RM, Coric V, Chen S, Zloza A, Vieth J, Mehnert JM, Malhotra J (July 2022). "A phase Ib dose-escalation study of troriluzole (BHV-4157), an oral glutamatergic signaling modulator, in combination with nivolumab in patients with advanced solid tumors". European Journal of Medical Research. 27 (1): 107. doi: 10.1186/s40001-022-00732-w . PMC   9250196 . PMID   35780243.
  6. Pfitzer J, Pinky PD, Perman S, Redmon E, Cmelak L, Suppiramaniam V, Coric V, Qureshi IA, Gramlich MW, Reed MN (August 2024). "Troriluzole rescues glutamatergic deficits, amyloid and tau pathology, and synaptic and memory impairments in 3xTg-AD mice". Journal of Neurochemistry. doi:10.1111/jnc.16215. PMID   39214859.
  7. "New Drug Shows Promise in Reversing Memory Loss and Cognitive Decline". SciTech (magazine) . September 5, 2024. Retrieved September 6, 2024.