Therapy Type: Small Molecule (timeline)
Target Type: Cholinergic System (timeline), Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 1)
Company: Suven Life Sciences Ltd
SUVN-G3031 is an orally active histamine H3 receptor antagonist being developed to treat cognitive deficits in Alzheimer's disease and schizophrenia. Histamine H3 receptors are widely expressed in healthy and Alzheimer's disease brains (Medhurst et al., 2009). They exert neuromodulatory functions on the cholinergic, adrenergic, and dopaminergic neurotransmitter systems. Preclinically, inhibiting this receptor has been shown in mice and rats to enhance cholinergic signaling, reduce tau phosphorylation, and reverse behavioral deficits (Medhurst et al., 2007; Bitner et al., 2011). Previous histamine H3 receptor antagonists that were in Phase 2 clinical development for cognition in Alzheimer's include Servier's S 38093, ABT 288, and GSK239512.
No peer-reviewed scientific studies have been published for SUVN-G3031. At the 2014 AAIC conference, Suven Life Sciences reported positive data on exposure, safety, pharmacokinetics, and behavioral assays in rats. The poster claimed an increase in cortical histamine and acetylcholine levels as well as reversal of memory deficits (Babu et al., 2014). Further preclinical data were presented at AAIC in 2015 (Benade et al., 2015).
Between September 2014 and August 2015, CRO Quintiles conducted a Phase 1 safety, tolerability, and pharmacokinetics study in 64 healthy men in the state of Kansas. This was a single- and multiple-ascending dose trial.
For registered trials on this compound, see clinicaltrials.gov.
- Medhurst AD, Roberts JC, Lee J, Chen CP, Brown SH, Roman S, Lai MK. Characterization of histamine H3 receptors in Alzheimer's Disease brain and amyloid over-expressing TASTPM mice. Br J Pharmacol. 2009 May;157(1):130-8. PubMed.
- Medhurst AD, Atkins AR, Beresford IJ, Brackenborough K, Briggs MA, Calver AR, Cilia J, Cluderay JE, Crook B, Davis JB, Davis RK, Davis RP, Dawson LA, Foley AG, Gartlon J, Gonzalez MI, Heslop T, Hirst WD, Jennings C, Jones DN, Lacroix LP, Martyn A, Ociepka S, Ray A, Regan CM, Roberts JC, Schogger J, Southam E, Stean TO, Trail BK, Upton N, Wadsworth G, Wald JA, White T, Witherington J, Woolley ML, Worby A, Wilson DM. GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimer's disease brain and improves cognitive performance in preclinical models. J Pharmacol Exp Ther. 2007 Jun;321(3):1032-45. PubMed.
- Bitner RS, Markosyan S, Nikkel AL, Brioni JD. In-vivo histamine H3 receptor antagonism activates cellular signaling suggestive of symptomatic and disease modifying efficacy in Alzheimer's disease. Neuropharmacology. 2011 Feb-Mar;60(2-3):460-6. PubMed.
- Babu MR, Nageswararao Muddana N, Mekala VR, P Jayarajan, Kanamarlapudi VB, Faheem MA, A, Irappanavar S, Goyal VK, Pandey SK, Gangadasari PN, Ponnamaneni R, Nirogi R. SUVN-G3031: A Novel and Potent Histamine H3 Receptor Antagonist for Potential Treatment of Cognitive Deficits. July 2014, Volume 10, Issue 4, Supplement, Pages P459–P460
- Benade VS, Saivishal Daripelli S, Thentu JB, Manoharan A, Medapati RB, Subramanian R, Mekala VR, Shinde AK, Badange RK, Goyal VK, Pandey SK, Nirogi R. Suvn-g3031, an h3 receptor inverse agonist, produces procognitive effects without affecting sleep in preclinical models. July 2015, Volume 11, Issue 7, Supplement, Page 475
No Available Further Reading