Delving into the Latest Updates on Samelisant with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

H3 receptor

Mechanism

H3 receptor antagonists(Histamine H3 receptor antagonists)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication

CataplexyNarcolepsyCognitive Dysfunction

Inactive Indication-

Originator Organization

Suven Life Sciences Ltd.

Active Organization

Suven Life Sciences Ltd.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC21H31N3O3

InChIKeyLNXDUSQEXVQFGP-UHFFFAOYSA-N

CAS Registry1394808-82-2

View All Structures (2)

Author: Jetta, Satish ; Kalaikadhiban, Ilayaraja ; Dogiparti, Dhanunjay Kumar ; Mohammed, Abdul Rasheed ; Shinde, Anil ; Bogan, Richard K. ; Jasti, Venkat ; Pandey, Santosh Kumar ; Chowdary Palacharla, Veera Raghava ; Abraham, Renny ; Benade, Vijay ; Bogan, Richard K ; Subramanian, Ramkumar ; Jayarajan, Pradeep ; Goyal, Vinod Kumar ; Ravula, Jyothsna ; Nirogi, Ramakrishna

Narcolepsy is a rare, chronic neurological disorder characterized by a dysregulated sleep-wake cycle, with core clinical features including excessive daytime sleepiness (EDS), cataplexy, hypnopompic/hypnagogic hallucinations, and sleep paralysis. Several treatment options are available for the symptomatic management of narcolepsy, but they have limitations. Comorbidities of narcolepsy further limit the treatment choices. Blocking of histamine 3 (H3) receptors has been demonstrated to be a viable approach for the management of symptoms of narcolepsy. Samelisant (SUVN-G3031) is a new H3 receptor inverse agonist. The efficacy, safety, tolerability, and pharmacokinetics of Samelisant in narcolepsy patients were evaluated in a phase 2, double-blind, placebo-controlled study (ClinicalTrials.gov identifier: NCT04072380). Patients diagnosed with narcolepsy according to the International Classification of Sleep Disorders criteria and having an Epworth Sleepiness Scale (ESS) score of ≥12 and a mean Maintenance of Wakefulness Test (MWT) time of <12 min across the 4 sessions at baseline were enrolled. The total study duration was up to 7 weeks, which included a screening period of 4 weeks, a treatment period of 2 weeks, and a safety follow-up 1 week after the last study drug administration. The primary efficacy measure was the change in total ESS score compared to placebo. Secondary and exploratory assessments included the Clinical Global Impression of Severity, MWT, Clinical Global Impression of Change, Patient Global Impression of Change and cataplexy rate. Safety assessments included monitoring adverse events (AEs) and laboratory assessments. Of the 426 patients screened, 190 were randomized. The safety and intention-to-treat population included 188 and 164 patients, respectively. A statistically significant treatment effect of Samelisant was observed on the primary endpoint, indicating improvements in EDS. The treatment's impact on EDS was also evident on the other patients' and clinicians' perspectives scales. The AEs reported in ≥5 % patients in any treatment groups were insomnia, abnormal dreams, nausea, and hot flush. Global phase 3 studies and long-term safety and efficacy assessments of Samelisant are planned to reaffirm the current findings.

01 Jun 2021·PsychopharmacologyQ3 · MEDICINE

Samelisant (SUVN-G3031), a potent, selective and orally active histamine H3 receptor inverse agonist for the potential treatment of narcolepsy: pharmacological and neurochemical characterisation

Q3 · MEDICINE

Article

Author: Subramanian, Ramkumar ; Badange, Rajesh ; Jasti, Venkat ; Benade, Vijay ; Jayarajan, Pradeep ; Petlu, Surendra ; Shinde, Anil ; Daripelli, Saivishal ; Kamuju, Venkatesh ; Muddana, Nageswara Rao ; Bhyrapuneni, Gopinadh ; Mekala, Venkat Reddy ; Nirogi, Ramakrishna

RATIONALESamelisant (SUVN-G3031) is a potent and selective histamine H3 receptor (H3R) inverse agonist with good brain penetration and oral bioavailability.OBJECTIVESPharmacological and neurochemical characterisation to support the utility of Samelisant (SUVN-G3031) in the treatment of sleep-related disorders like narcolepsy.METHODSSamelisant (SUVN-G3031) was tested in rat brain microdialysis studies for evaluation of modulation in histamine, dopamine and norepinephrine. Sleep EEG studies were carried out in orexin knockout mice to study the effects of Samelisant (SUVN-G3031) on the sleep-wake cycle and cataplexy.RESULTSSamelisant (SUVN-G3031) has a similar binding affinity towards human (hH3R; K_i = 8.7 nM) and rat (rH3R; K_i = 9.8 nM) H3R indicating no inter-species differences. Samelisant (SUVN-G3031) displays inverse agonist activity and it exhibits very high selectivity towards H3R. Samelisant (SUVN-G3031) treatment in mice produced a dose-dependent increase in tele-methylhistamine levels indicating the activation of histaminergic neurotransmission. Apart from increasing the levels of histamine, Samelisant (SUVN-G3031) also modulates dopamine and norepinephrine levels in the cerebral cortex while it has no effects on dopamine levels in the striatum or nucleus accumbens. Treatment with Samelisant (SUVN-G3031; 10 and 30 mg/kg, p.o.) produced a significant increase in wakefulness with a concomitant decrease in NREM sleep in orexin knockout mice subjected to sleep EEG. Samelisant (SUVN-G3031) also produced a significant decrease in Direct REM sleep onset (DREM) episodes, demonstrating its anticataplectic effects in an animal model relevant to narcolepsy. Modulation in cortical levels of histamine, norepinephrine and dopamine provides the neurochemical basis for wake-promoting and anticataplectic effects observed in orexin knockout mice.CONCLUSIONSPre-clinical studies of Samelisant (SUVN-G3031) provide a strong support for utility in the treatment of sleep-related disorders related to EDS and is currently being evaluated in a phase 2 proof of concept study in the USA for the treatment of narcolepsy with and without cataplexy.

01 Jun 2021·Journal of PsychopharmacologyQ3 · MEDICINE

Histamine 3 receptor inverse agonist Samelisant (SUVN-G3031): Pharmacological characterization of an investigational agent for the treatment of cognitive disorders

Q3 · MEDICINE

Article

Author: Shinde, Anil ; Jayarajan, Pradeep ; Ganuga, Narender ; Petlu, Surendra ; Manoharan, Arunkumar ; Bhyrapuneni, Gopinadh ; Jasti, Venkat ; Medapati, Rajesh B ; Subramanian, Ramkumar ; Abraham, Renny ; Badange, Rajesh K ; Benade, Vijay ; Nirogi, Ramakrishna ; Grandhi, Venkata R ; Gandipudi, Sudhakar

Background: Central histamine H3 receptors are a family of presynaptic auto and heteroreceptors. Blockade of the presynaptic H3 receptors activates the downstream pathway(s) involved in the processes of learning and memory, making it a potential therapeutic option for ameliorating cognitive dysfunction. Samelisant (SUVN-G3031) is a potent and selective inverse agonist at the H3 receptors. Aim: The aim of this research is to study the effects of Samelisant in diverse animal models of cognitive functions. Methods: The effects of Samelisant on cognitive functions were studied using social recognition, object recognition and Morris water maze tasks. Neurochemical and electrophysiological effects of Samelisant were monitored using microdialysis and electroencephalography techniques. Results: Samelisant showed procognitive effects in diverse animal models of cognition at doses ranging from 0.3 to 3 mg/kg, per os ( p.o.) (social recognition and object recognition task). Samelisant significantly increased the brain acetylcholine levels in the cortex at doses of 10 and 20 mg/kg, p.o. In the Morris water maze task, combined administration of suboptimal doses of Samelisant and donepezil resulted in procognitive effects significantly larger than the either treatment. Similarly, Samelisant significantly potentiated the effects of donepezil on pharmacodynamic biomarkers of cognition i.e. acetylcholine levels in brain and neuronal theta oscillations. Conclusion: Samelisant may have potential utility in the treatment of cognitive deficits associated with hypocholinergic state.

100 Deals associated with Samelisant

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14835

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cataplexy	Phase 2	CA	Suven Life Sciences Ltd.	21 Sep 2019
Cataplexy	Phase 2	US	Suven Life Sciences Ltd.	21 Sep 2019
Narcolepsy	Phase 2	-	Suven Life Sciences Ltd.	-
Cognitive Dysfunction	Phase 1	US	Suven Life Sciences Ltd.	-
Cognition Disorders	Discovery	US	Suven Life Sciences Ltd.	01 Sep 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02342041 \| NCT04072380 (Pubmed \| Clin Drug Investig)	Not Applicable	Narcolepsy	-	SUVN-G3031	hwkrcudsod(qesfkppxmg) = cvkeaqaodm unuplxvbrg (izmiltsrqj )	-	01 Jul 2020
NCT04072380 (SUVN-G3031, WSC2019)	Phase 2	Narcolepsy	-	SUVN-G3031	qodgoxttpl(pmfvknwhbp) = indicated superior wake promoting profile of SUVN-G3031 ocsbiqdyhs (bcffpaeoad ) View more	Positive	20 Sep 2019
SUVN-G3031 (AAIC2014)	Not Applicable	Cognitive Dysfunction	-	SUVN-G3031	ulzrabkqlo(zdumtucipd) = lhpzcgegfl byghgicjwa (zaxswyserg ) View more	-	01 Jul 2014