Intepirdine

Last updated
Intepirdine
Intepirdine.svg
Clinical data
Other namesSB-742457, RVT-101
Routes of
administration
Oral
ATC code
  • none
Legal status
Legal status
  • Investigational/abandoned
Identifiers
  • 3-Phenylsulfonyl-8-(piperazin-1-yl)quinoline
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.158.094 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H19N3O2S
Molar mass 353.44 g·mol−1
3D model (JSmol)
  • C3CNCCN3c1cccc(c1nc4)cc4S(=O)(=O)c2ccccc2
  • InChI=1S/C19H19N3O2S/c23-25(24,16-6-2-1-3-7-16)17-13-15-5-4-8-18(19(15)21-14-17)22-11-9-20-10-12-22/h1-8,13-14,20H,9-12H2 X mark.svgN
  • Key:JJZFWROHYSMCMU-UHFFFAOYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Intepirdine (INN; developmental codes SB-742457, RVT-101) [1] is a selective 5-HT6 receptor antagonist with potential cognition, memory, and learning-enhancing effects. [2] [3] It was under development by GlaxoSmithKline for the treatment of Alzheimer's disease and demonstrated some preliminary efficacy in phase II clinical trials. [3] GSK chose not to continue development and sold the rights to Axovant Sciences for $5 million in December 2014. [4]

Results of a phase III clinical trial for the treatment of Alzheimer's disease were reported in September 2017. [5] The trial showed no improvement over control group and Axovant lost 70% of its value upon the announcement of the trial results. [6]

Intepirdine also entered clinical trials for dementia with Lewy bodies, also with negative results. [7] Consequently, Axovant announced in 2018 that it has discontinued development of this drug. [7]

Related Research Articles

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

Memantine is a medication used to slow the progression of moderate-to-severe Alzheimer's disease. It is taken by mouth.

Neurocrine Biosciences, Inc. is an American biopharmaceutical company founded in 1992. The company is headquartered in San Diego, California, and led by CEO Kevin Gorman. Neurocrine develops treatments for neurological and endocrine-related diseases and disorders. In 2017, the company's drug valbenazine (Ingrezza) was approved in the US to treat adults with tardive dyskinesia (TD).

<span class="mw-page-title-main">Latrepirdine</span> Antihistamine drug

Latrepirdine is an antihistamine drug which has been used clinically in Russia since 1983.

5-HT<sub>6</sub> receptor Protein-coding gene in the species Homo sapiens

The 5HT6 receptor is a subtype of 5HT receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5HT). It is a G protein-coupled receptor (GPCR) that is coupled to Gs and mediates excitatory neurotransmission. HTR6 denotes the human gene encoding for the receptor.

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

Homotaurine is a natural sulfonic acid found in seaweed. It is analogous to taurine, but with an extra carbon in its chain. It has GABAergic activity, apparently by mimicking GABA, which it resembles.

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

Casopitant (INN), former tentative trade names Rezonic (U.S.) and Zunrisa (Europe), is an NK1 receptor antagonist which was undergoing research for the treatment of chemotherapy-induced nausea and vomiting. It was under development by GlaxoSmithKline. In July 2008, the company filed a marketing authorisation application with the European Medicines Agency. The application was withdrawn and development was discontinued in September 2009 because GlaxoSmithKline decided that further safety assessment was necessary. However, a 2022 review listed casopitant as under development as a potential novel antidepressant for the treatment of major depressive disorder, with a phase 2 clinical trial having been completed.

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

Lecozotan is an investigational drug by Wyeth tested for improvement of cognitive functions of Alzheimer's disease patients. As of June 2008, the first Phase III clinical trial has been completed.

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

Pimavanserin, sold under the brand name Nuplazid, is an atypical antipsychotic which is approved for the treatment of Parkinson's disease psychosis and is also being studied for the treatment of Alzheimer’s disease psychosis, schizophrenia, agitation, and major depressive disorder. Unlike other antipsychotics, pimavanserin is not a dopamine receptor antagonist.

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

Ecopipam is a dopamine antagonist which is under development for the treatment of Lesch-Nyhan syndrome, Tourette's syndrome, speech disorders, and restless legs syndrome. It is taken by mouth.

Idalopirdine (INN) (code names Lu AE58054,) is a potent and selective 5-HT6 receptor antagonist under development by Lundbeck as an augmentation therapy for the treatment of cognitive deficits associated with Alzheimer's disease and schizophrenia. As of October 2013 it is in phase III clinical trials.

<span class="mw-page-title-main">PRX-07034</span> Chemical compound

PRX-07034 is a selective 5-HT6 receptor antagonist. It has cognition and memory-enhancing properties and potently decreases food intake and body weight in rodents. PRX-07034 was under development by Epix Pharmaceuticals for the treatment of obesity and cognitive impairment associated with Alzheimer's disease and schizophrenia but upon the company collapsing due to lack of funds the compound was auctioned to another corporation.

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

Cerlapirdine is a drug which was under development by Wyeth/Pfizer for the treatment of cognitive disorders associated with Alzheimer's disease and schizophrenia. In a phase II clinical trial it demonstrated a trend toward efficacy along with a good side effect profile and no incidence of serious adverse events, but no further development has occurred since 2011.

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

Brexpiprazole, sold under the brand name Rexulti among others, is a medication used for the treatment of major depressive disorder, schizophrenia, and agitation associated with dementia due to Alzheimer's disease. It is an atypical antipsychotic.

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

Piromelatine (Neu-P11) is a multimodal sleep drug under development by Neurim Pharmaceuticals. It is an agonist at melatonin MT1/MT2 and serotonin 5-HT1A/5-HT1D receptors. Neurim is conducting a phase II randomized, placebo controlled trial of cognitive and sleep effects in Alzheimer's disease.

<span class="mw-page-title-main">AVN-211</span> Chemical compound

AVN-211 (CD-008-0173) is a drug which acts as a highly selective 5-HT6 receptor antagonist and is under development by Avineuro Pharmaceuticals for the treatment of schizophrenia. In early 2011, it successfully completed phase IIa clinical trials, with benefits on positive symptoms and some procognitive effects observed, and in mid 2013, phase IIb clinical trials for schizophrenia began. Avineuro Pharmaceuticals also expressed intention to start clinical trials of AVN-211 for Alzheimer's disease in 2015.

<span class="mw-page-title-main">Brilaroxazine</span> Experimental atypical antipsycotic

Brilaroxazine, also known as oxaripiprazole, is an investigational atypical antipsychotic which is under development by Reviva Pharmaceuticals for the treatment neuropsychiatric and inflammatory disorders. As of July 2023, it is in phase III clinical trials for schizophrenia. Reviva Pharmaceuticals also intends to investigate brilaroxazine for the treatment of bipolar disorder, major depressive disorder, attention deficit hyperactivity disorder (ADD/ADHD), psychosis/agitation associated with Alzheimer's disease, Parkinson's disease psychosis, as well as the inflammatory disorders pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), and psoriasis. The FDA granted brilaroxazine orphan drug designation for the treatment of PAH and IPF.

<span class="mw-page-title-main">AVN-101</span> Chemical compound

AVN-101, a close structural analogue of latrepirdine, is a selective 5-HT6 receptor antagonist which is under development by Avineuro Pharmaceuticals for the treatment of Alzheimer's disease and anxiety disorders. As of November 2013, it was in phase II clinical trials for these indications.

<span class="mw-page-title-main">Sio Gene Therapies</span> American pharmaceutical company

Sio Gene Therapies, formerly known as Axovant Gene Therapies, is a clinical-stage pharmaceutical company that develops gene therapies to treat neurological disorders. The company is headquartered in New York City and is incorporated in Basel, Switzerland. The company was founded by former hedge fund analyst Vivek Ramaswamy in 2014 as a wholly owned subsidiary of Roivant Sciences.

<span class="mw-page-title-main">SAGE-718</span> Chemical compound

SAGE-718 is experimental drug being investigated for the treatment of neurological disorders and cognitive impairment. It acts as a positive allosteric modulator of the NMDA receptor, whose activity is essential for learning, memory, and cognition. SAGE-718 is an analog of the neurosteroid 24S-hydroxycholesterol.

<span class="mw-page-title-main">AVN-322</span> Chemical compound

AVN-322 is a 5-hydroxytryptamine subtype 6 receptor antagonist manufactured by Avineuro Pharmaceuticals Inc. that could potentially be used to combat Alzheimer's disease and schizophrenia. AVN-322 also reverses the negative effects of scopolamine and MK-80.

References

  1. "Intepirdine - Axovant Sciences / GlaxoSmithKline". AdisInsight. Retrieved 9 January 2018.
  2. Upton N, Chuang TT, Hunter AJ, Virley DJ (July 2008). "5-HT6 receptor antagonists as novel cognitive enhancing agents for Alzheimer's disease". Neurotherapeutics. 5 (3): 458–69. doi:10.1016/j.nurt.2008.05.008. PMC   5084247 . PMID   18625457.
  3. 1 2 Rossé G, Schaffhauser H (February 2010). "5-HT(6) Receptor Antagonists as Potential Therapeutics for Cognitive Impairment". Current Topics in Medicinal Chemistry. 10 (2): 207–21. doi:10.2174/156802610790411036. PMID   20166958.
  4. Lowe, Derek (12 May 2015). "An Alzheimer's IPO, Because Why Not". In the Pipeline.
  5. Fiore, Kristina (27 September 2016). "NeuroBreak: Alzheimer's Drug Bombs; Elephant Tranquilizer ODs". MedPage Today.
  6. Garde, Damian (26 September 2017). "Another Alzheimer's failure: Axovant's drug flops in late-stage trial". STAT.
  7. 1 2 Taylor, Phil (Jan 8, 2018). "Axovant slumps as it dumps lead drug intepirdine". Fierce Biotech.