One of the oldest and most widely used commercial enzyme inhibitors is aspirin, which selectively inhibits one of the enzymes involved in the synthesis of molecules that trigger inflammation. 31566-31-1, you can contact me at any time and look forward to more communication. Name: Glyceryl monostearate.
Enzyme inhibitors cause a decrease in the reaction rate of an enzyme-catalyzed reaction by binding to a specific portion of an enzyme and thus slowing or preventing a reaction from occurring. 31566-31-1, Name is Glyceryl monostearate, molecular formula is C21H42O4, belongs to quinuclidine compound, is a common compound. In a patnet, author is Ford, Benjamin M., once mentioned the new application about 31566-31-1, Name: Glyceryl monostearate.
Reduced Tolerance and Asymmetrical Crosstolerance to Effects of the Indole Quinuclidinone Analog PNR-4-20, a G Protein-Biased Cannabinoid 1 Receptor Agonist in Mice: Comparisons with Delta(9)-Tetrahydrocannabinol and JWH-018
Most cannabinoid 1 receptor (CB1R) agonists will signal through both G protein-dependent and -independent pathways in an unbiased manner. Recruitment of beta-arrestin 2 desensitizes and internalizes receptors, producing tolerance that limits therapeutic utility of cannabinoids for chronic conditions. We developed the indole quinuclidinone (IQD) analog (Z)-2-((1-(4-fluorobenzyl)1H-indol-3-yl)nnethylene)quinuclidin-3-one (PNR-4-20) as a novel G protein-biased agonist at CB(1)Rs, and the present studies determine if repeated administration of PNR-4-20 produces lesser tolerance to in vivo effects compared with unbiased CB1R agonists, Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and 1-pentyl-3-(1-naphthoyl)indole (JWH-018). Adult male National Institutes of Health Swiss mice were administered comparable doses of PNR-4-20 (100 mg/kg), Delta(9)-THC (30 mg/kg), or JWH-018 (3 mg/kg) once per day for five consecutive days to determine tolerance development to hypothermic, antinociceptive, and cataleptic effects. Persistence of tolerance was then determined after a drug abstinence period. We found that unbiased CB1R agonists Delta(9)-THC and JWH-018 produced similar tolerance to these effects, but lesser tolerance was observed with PNR-4-20 for hypothermic and cataleptic effects. Tolerance to the effects of PNR-4-20 completely recovered after drug abstinence, while residual tolerance was always observed with unbiased CB1R agonists. Repeated treatment with PNR-4-20 and Delta(9)-THC produced asymmetric cross-tolerance to hypothermic effects. Importantly, binding studies suggest PNR-4-20 produced significantly less down-regulation of CB(1)Rs relative to Delta(9)-THC in hypothalamus and thalamus of chronically treated mice. These studies suggest that the G protein-biased CB1R agonist PNR-4-20 produces significantly less tolerance than unbiased cannabinoid agonists, and that the IQD analogs should be investigated further as a novel molecular scaffold for development of new therapeutics.
One of the oldest and most widely used commercial enzyme inhibitors is aspirin, which selectively inhibits one of the enzymes involved in the synthesis of molecules that trigger inflammation. 31566-31-1, you can contact me at any time and look forward to more communication. Name: Glyceryl monostearate.
Reference:
Quinuclidine – Wikipedia,
,Quinuclidine | C7H13N | ChemSpider