scholarly journals Methamphetamine- and 3,4-Methylenedioxymethamphetamine–Induced Behavioral Changes in Histamine H3–Receptor Knockout Mice

2009 ◽  
Vol 111 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Tomohiro Okuda ◽  
Dongying Zhang ◽  
He Shao ◽  
Nobuyuki Okamura ◽  
Naoko Takino ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Behavioral Changes ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

005 Samelisant (SUVN-G3031), a histamine H3 receptor inverse agonist in animal models of sleep disorders

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A2-A2
Author(s):  
Saivishal Daripelli ◽  
Parusharamulu Molgara ◽  
Nageswararao Muddana ◽  
Pradeep Jayarajan ◽  
Venkat Reddy Mekala ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Radioligand Binding ◽  
Research Work ◽  
Brain Regions ◽  
Inverse Agonist ◽  
Abuse Liability ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

Abstract Introduction Narcolepsy is a chronic sleep disorder characterized by overwhelming daytime drowsiness, sudden attacks of sleep and sometimes accompanied by cataplexy. Although the orexin deficiency is considered to be the primary cause of this disorder, lot of attention has been diverted on targeting histaminergic neurotransmission by blockade of histamine H3 receptor (H3R). Samelisant (SUVN-G3031) is one of the potent and selective H3R inverse agonist currently being evaluated in a Phase 2 study as monotherapy for the treatment of narcolepsy with and without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). In the current research work, Samelisant was evaluated for neurotransmitter changes in rats and sleep EEG in orexin knockout mice, a reliable proof-of-concept study for treatment of excessive daytime sleepiness and cataplexy in narcolepsy. Methods Binding affinity of Samelisant towards human and rat histamine H3R was evaluated in in-vitro radioligand binding assay and functionality in GTP□S assay. Effect of Samelisant was studied in (R)-α-methyl histamine induced dipsogenia. In rat brain microdialysis, Samelisant was evaluated for its effects on modulation of neurotransmitters like histamine, dopamine and norepinephrine. Male orexin knockout mice were implanted with telemetric device for simultaneous monitoring of electroencephalography (EEG) and electromyography. Effects of Samelisant (3 and 10 mg/kg, p.o.) were evaluated during active period of animals. Results Samelisant is an inverse agonist at histamine H3 receptors with hKi of 8.7 nM and showed minimal binding against over 70 target sites. Samelisant produced significant increase in histamine, dopamine and norepinephrine levels in cortex. Samelisant produced no change in the striatal and accumbal dopamine levels in rats, suggesting no propensity to induce abuse liability. Samelisant blocked R-α-methyl histamine induced water intake and produced dose dependent increase in tele-methylhistamine levels in various brain regions and in cerebrospinal fluid of male Wistar rats. Samelisant produced significant increase in wakefulness with concomitant decrease in non-rapid eye movement sleep in orexin knockout mice. Samelisant also significantly decreased number of cataplectic episodes in orexin knockout mice. Conclusion Samelisant is an inverse agonist at histamine H3 receptor and results from the preclinical studies presented here provide a strong evidence for the potential utility of Samelisant in the treatment of narcolepsy with and without cataplexy. Support (if any):

scholarly journals 0008 SUVN-G3031, A Histamine H3 Receptor Inverse Agonist Produces Robust Wake Promoting and Anticataplectic Activity in Orexin Knockout Mice

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A3-A3
Author(s):  
V Benade ◽  
S Daripelli ◽  
S Petlu ◽  
R Subramanian ◽  
G Bhyrapuneni ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Animal Studies ◽  
Preclinical Study ◽  
Inverse Agonist ◽  
Strong Basis ◽  
Histamine H3 Receptor ◽  
Histaminergic Neurons ◽  
H3 Receptor ◽  
Receptor Inverse Agonist ◽  
Histamine H3

Abstract Introduction Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, sleep paralysis, hallucinations, and in some cases episodes of cataplexy. Results from animal studies indicate the involvement of deficient orexin transmission in narcolepsy which can be circumvented by the activation of histaminergic neurons. SUVN-G3031 is a potent and selective histamine H3 receptor inverse agonist with hKi of 8.7 nM and shows less than 50% inhibition at 1 µM against 70 other targets. SUVN-G3031 exhibited excellent pharmacokinetic properties and brain penetration in preclinical species. Oral administration of SUVN-G3031 produces significant increase in histamine, dopamine and norepinephrine levels in the rat cortex. Long-term safety studies in animals have been successfully completed without any concern for further development of SUVN-G3031. In the present study, the effects of SUVN-G3031 were evaluated in orexin knockout mice, a reliable animal model of narcolepsy as a proof-of-concept study for the treatment of narcolepsy with and without cataplexy. Methods Male orexin knockout mice (10 - 15 weeks old, 25 - 35 g at the time of surgery) were implanted with telemetric device for simultaneous monitoring of electroencephalography (EEG) and electromyography. Animals were allowed surgical recovery of 3 weeks prior to EEG recording. Effects of SUVN-G3031 (3 and 10 mg/kg, p.o.) were evaluated during active period of animals. Results SUVN-G3031 produced significant increase in wakefulness with concomitant decrease in non-rapid eye movement sleep in orexin knockout mice. SUVN-G3031 also significantly decreased the number of cataplectic episodes in orexin knockout mice. Conclusion Results from the current preclinical study provide a strong basis for the utility of SUVN-G3031 for the treatment of narcolepsy with and without cataplexy. SUVN-G3031 is currently being evaluated in a Phase 2 study as monotherapy for the treatment of narcolepsy with and without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). Support None

Impaired drinking response in histamine H3 receptor knockout mice following dehydration or angiotensin-II challenge

2006 ◽  
Vol 84 (3) ◽  
pp. 504-510 ◽  
Author(s):  
Ryo Yoshimoto ◽  
Yasuhisa Miyamoto ◽  
Kazuhiko Takahashi ◽  
Hidehito Kotani ◽  
Akio Kanatani ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Knockout Mice ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Drinking Response ◽  
Histamine H3

Enhanced morphine-induced antinociception in histamine H3 receptor gene knockout mice

2009 ◽  
Vol 57 (4) ◽  
pp. 409-414 ◽  
Author(s):  
Jalal Izadi Mobarakeh ◽  
Kazuhiro Takahashi ◽  
Kazuhiko Yanai
Keyword(s):  
Knockout Mice ◽  
Gene Knockout ◽  
Receptor Gene ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Gene Knockout Mice ◽  
Histamine H3

Diether (substituted) piperidine derivatives as novel, histamine H3 receptor ligands

2009 ◽  
Vol 58 (S1) ◽  
pp. 47-48
Author(s):  
K. J. Kuder ◽  
X. Ligneau ◽  
J.-C. Camelin ◽  
D. Łażewska ◽  
J.-C. Schwartz ◽  
...  
Keyword(s):  
Receptor Ligands ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

scholarly journals Purification of a histamine H3 receptor negatively coupled to phosphoinositide turnover in the human gastric cell line HGT1.

1992 ◽  
Vol 267 (35) ◽  
pp. 25315-25320
Author(s):  
Y Cherifi ◽  
C Pigeon ◽  
M Le Romancer ◽  
A Bado ◽  
F Reyl-Desmars ◽  
...  
Keyword(s):  
Cell Line ◽  
Histamine H3 Receptor ◽  
Gastric Cell ◽  
Phosphoinositide Turnover ◽  
H3 Receptor ◽  
Histamine H3

Ameliorating effects of histamine H3 receptor antagonist E177 on acute pentylenetetrazole-induced memory impairments in rats

2021 ◽  
Vol 405 ◽  
pp. 113193
Author(s):  
Alaa Alachkar ◽  
Mohamed Lotfy ◽  
Ernest Adeghate ◽  
Dorota Łażewska ◽  
Katarzyna Kieć-Kononowicz ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Histamine H3 Receptor ◽  
Memory Impairments ◽  
H3 Receptor ◽  
Histamine H3

Chronic administration of the histamine H3 receptor agonist immepip decreases l-Dopa-induced dyskinesias in 6-hydroxydopamine-lesioned rats

2019 ◽  
Vol 236 (6) ◽  
pp. 1937-1948 ◽  
Author(s):  
Alberto Avila-Luna ◽  
Camilo Ríos ◽  
Arturo Gálvez-Rosas ◽  
Sergio Montes ◽  
José-Antonio Arias-Montaño ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Chronic Administration ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
6 Hydroxydopamine ◽  
Histamine H3
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