1. Home
  2. Knowledge Base
  3. References
  4. SUVN-G3031, H3 receptor inverse agonist produces wake promoting activity in rats with hypocretin-2-saporin lesions of the lateral hypothalamus

SUVN-G3031, H3 receptor inverse agonist produces wake promoting activity in rats with hypocretin-2-saporin lesions of the lateral hypothalamus

Daripelli S, Bhayrapuneni G, Tirumalesetty C, Benade V, Subramanian R, Petlu S, Praveena N, Jayarajan P, Shinde A, Badange R, Bhatta V, Nirogi R (2018) SUVN-G3031, H3 receptor inverse agonist produces wake promoting activity in rats with hypocretin-2-saporin lesions of the lateral hypothalamus. Neuroscience 2018 Abstracts 679.23 / VV4. Society for Neuroscience, San Diego, CA.

Summary: Numerous studies have demonstrated that brain histamine plays a crucial role in maintenance of wakefulness, attention, learning and other cognitive processes. SUVN-G3031, a potent H3 receptor inverse agonist is being developed for the treatment of narcolepsy and other sleep related disorders. SUVN-G3031 is one of the lead molecules with hKi of 8.7 nM and has more than 100 fold selectivity against the related GPCRs. SUVN-G3031 exhibited desired pharmacokinetic properties and brain penetration. SUVN-G3031 blocked R-α-methylhistamine induced water intake and increased tele-methylhistamine levels in brain and cerebrospinal fluid. A single oral administration of SUVN-G3031 produced significant increase in acetylcholine, histamine, dopamine and norepinephrine levels in the cortex. SUVN-G3031 produced wake promoting activity in male Wistar rats. In the present study, effects of SUVN-G3031 on sleep/ wake profile were evaluated in rats with lateral hypothalamic lesion using neurotoxin hypocretin-2-saporin. Narcoleptic-like sleep behavior was observed in rats injected with hypocretin-2-saporin in lateral hypothalamus. SUVN-G3031 produced significant increase in wakefulness with concomitant decrease in rapid eye movement (REM) sleep in these animals. These results are in agreement with electroencephalography (EEG) studies carried out in healthy male Wistar rats. Results from the current study and the neurotransmitter modulations produced by SUVN-G3031 provide a strong basis for the potential of SUVN-G3031 in treatment of sleep related disorders. First in human, Phase 1 studies for SUVN-G3031 are completed underUS IND and SUVN-G3031 has shown desirable pharmacokinetic profile with safety and tolerability in healthy human volunteers. Phase 2 study for narcolepsy is currently being planned.

Related Products: Orexin-B-SAP (Cat. #IT-20)