H3 receptor modulation of the release of neurotransmitters in vivo

1998 ◽  
pp. 27-40 ◽  
Author(s):  
P. Blandina ◽  
L. Bacciottini ◽  
M.G. Giovannini ◽  
P.F. Mannaioni
Keyword(s):  
Receptor Modulation ◽  
H3 Receptor

In vivo andin vitro ethanol exposure in prenatal rat brain: GABAB receptor modulation on dopamine D1 receptor and protein kinase A

Synapse ◽  
2008 ◽  
Vol 62 (7) ◽  
pp. 534-543 ◽  
Author(s):  
H.Y. Lee ◽  
N. Naha ◽  
S.P. Li ◽  
M.J. Jo ◽  
M.L. Naseer ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Rat Brain ◽  
Gabab Receptor ◽  
Ethanol Exposure ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Receptor Modulation ◽  
Kinase A

ChemInform Abstract: Substituted N-Phenylcarbamates as Histamine H3 Receptor Antagonists with Improved in vivo Potency.

ChemInform ◽  
2010 ◽  
Vol 31 (24) ◽  
pp. no-no
Author(s):  
S. Reidemeister ◽  
H. Stark ◽  
X. Ligneau ◽  
C. R. Ganellin ◽  
J.-C. Schwartz ◽  
...  
Keyword(s):  
Receptor Antagonists ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

Corticosteroids decrease glomerular angiotensin receptors

1987 ◽  
Vol 252 (3) ◽  
pp. F453-F457 ◽  
Author(s):  
J. G. Douglas
Keyword(s):  
Mineralocorticoid Receptor ◽  
Mesangial Cells ◽  
Angiotensin Receptors ◽  
Electrolyte Balance ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Receptor Density ◽  
Receptor Modulation ◽  
Glomerular Hemodynamics

Angiotensin II (ANG II) receptors of glomerular mesangial cells are regulated in vivo by changes in Na balance, effects that are presumed to be secondary to changes in circulating ANG II. However, since changes in ANG II were accompanied by parallel changes in plasma aldosterone in all models tested, it is possible that aldosterone may have also participated in the modulation of glomerular ANG II receptors. To test this hypothesis, short-term aldosterone infusions within the physiological range were employed to favor actions that would be mediated through a high-affinity mineralocorticoid receptor. The glucocorticoid, dexamethasone, was also tested to determine the mineralocorticoid specificity of the response. Two infusion rates were associated with a decrease in glomerular ANG II receptor density of 33 and 45%, respectively. There were no changes in the affinity of ANG II in either tissue or in adrenal receptor density. Serum potassium and urinary Na/K ratio were lower in the aldosterone group. Spironolactone abolished the effect of aldosterone consistent with an action mediated through a specific mineralocorticoid receptor. Dexamethasone administration produced similar downregulation of glomerular ANG II receptor and was unaccompanied by a change in electrolyte balance or blood volume. These studies support the hypothesis that corticosteroids modulate glomerular ANG II receptors and validate the complexity of glomerular receptor modulation. The downregulation observed would be expected to diminish the ability of ANG II to influence glomerular hemodynamics in models such as mineralocorticoid and glucocorticoid-induced hypertension.

0155 SUVN-G3031, A Potent and Selective Histamine H3 Receptor Inverse Agonist - Differentiating Features Over Current Treatments of Narcolepsy

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A61-A61
Author(s):  
A Shinde ◽  
R Subramanian ◽  
R Palacharla ◽  
S Pandey ◽  
V Benade ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Abuse Liability ◽  
Species Variation ◽  
Pharmacological Agents ◽  
Histamine H3 Receptor ◽  
Inverse Agonists ◽  
H3 Receptor ◽  
Histamine H3

Abstract Introduction Majority of pharmacological agents used in the treatment of narcolepsy have several limitations. Both nonclinical and clinical evidences suggest usefulness of the histamine H3 receptor (H3R) inverse agonists for the treatment of narcolepsy and addressing several of the current limitations. Methods Extensive nonclinical studies were carried out for SUVN-G3031 and other pharmacological agents that are currently being used for the treatment of narcolepsy. Nonclinical parameters like inter-species binding affinity, selectivity profile, in vivo and in vitro ADME features, nonclinical efficacy, neurochemistry and safety were compared. Results SUVN-G3031 has no inter-species variation in binding affinity at H3R with less than 50% inhibition at 1 µM against 70 other targets. Unlike pitolisant, SUVN-G3031 has no significant binding affinity at sigma 1 and 2 receptor. SUVN-G3031 has no inhibition and induction liability towards major CYP enzymes and transporters. Pitolisant is reported to be a CYP3A4, CYP2B6, and CYP1A2 inducer and a CYP2D6 and OCT1 inhibitor. SUVN-G3031 has robust wake promoting effects. SUVN-G3031 showed negligible affinity towards hERG channel with IC50 > 10 µM and had no effects on any ECG parameters in dog telemetry study. SUVN-G3031 did not show convulsion in rats up to the tested dose of 100 mg/kg, p.o. Most of the pharmacological agents used for the treatment of narcolepsy have abuse liability; SUVN-G3031 produced no change in the striatal and accumbal dopamine levels in rats suggesting no propensity to induce abuse liability. Unlike competing H3R inverse agonists, SUVN-G3031 has no effects on fertility and embryo-fetal development up to the highest tested doses. Conclusion Nonclinical studies demonstrate superiority of SUVN-G3031 over pharmacological agents currently used in the treatment of narcolepsy. SUVN-G3031 is being evaluated in a Phase 2 study as monotherapy for the treatment of narcolepsy with and without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). Support None

Sign in / Sign up

Export Citation Format

Share Document