62-68-0 Usage
Description
PROADIFEN HYDROCHLORIDE is a nonspecific cytochrome P (CYP)450 inhibitor that demonstrates potent inhibitory effects on various CYP450 isoforms. It is known for its ability to potentiate the effects of many different drugs by inhibiting their metabolism, with IC50 values in the μM range when tested using human liver microsomes. Additionally, PROADIFEN HYDROCHLORIDE inhibits CYP450-dependent arachidonic acid conversion to active EET metabolites, antagonizes the recovery of functional calcium pools, and acts as a noncompetitive inhibitor of acetylcholine nicotinic receptors.
Used in Pharmaceutical Industry:
PROADIFEN HYDROCHLORIDE is used as a cytochrome P-450 inhibitor for its ability to block glibenclamide-sensitive K+ channels, inhibit neuronal nitric oxide synthetase, and stimulate endothelial cell prostacyclin while inhibiting platelet thromboxane synthesis.
Used in Cardiology:
PROADIFEN HYDROCHLORIDE is used as an antiarrhythmic agent for its good antiarrhythmic effects and its ability to substantially reduce the depletion of cardiac norepinephrine.
Used in Neurology:
PROADIFEN HYDROCHLORIDE is used as an inhibitor of NOS1, AChR, and KIR6.1 for its potential therapeutic applications in neurological disorders.
Safety Profile
Poison by intraperitoneal, subcutaneous, and intravenous routes. Moderately toxic by ingestion. Experimental reproductive effects. When heated to decomposition it emits very toxic fumes of NOx and HCl.
in vitro
previous study found that when incubated with human liver microsomes, skf525a could undergo cyp-dependent oxidative n-deethylation to its secondary amine metabolite skf8742. in addition, skf525a and its metabolite and primary amine analog all inhibited cyp2b6-, cyp2c9-, cyp2c19-, cyp2d6-, as well as cyp3a-selective reactions to various degrees but had little effect on cyp1a2, cyp2a6, and cyp2e1 reactions [1].
in vivo
animal study found that skf 525a at 1.5-9 mg/kg could reduce or abolish the hypertensive effect of mcn-a-343, dmpp and nicotine, but could neither noticeably affect the hypertensive effect of tyramine, adrenaline and noradrenaline, nor the hypotensive effect of acetylcholine and orciprenaline. thus, skf 525a was able to block the rat sympathetic ganglia and the adrenal medulla and such blockade was non-specific. moreover, the blockade might result from the stabilizing effect of skf 525a on postsynaptic membranes of the sympathetic ganglia and the adrenal medulla [2].
IC 50
in the μm range when tested using human liver microsomes
References
1) Franklin and Hathaway (2008)?2-Diethylaminoethyl-2,2-diphenylvalerate-HCL (SKF525A) revisited: comparative cytochrome P450 inhibition in human liver microsomes by SKF525A, its metabolites, and SKF-acid and SKF-alcohol;?Drug Metab. Dispos,?36?2539
2) Suarez-Kurtz and Bianchi (1970)?Sites of action of SKF-525A in nerve and muscle;?J. Pharmacol. Exp. Ther.,?172?33
3) Spitzmaul?et al. (2009)?The local anesthetics proadifen and adiphenine inhibit nicotinic receptors by different molecular mechanisms; Br. J. Pharmacol.,?157?804
4) Prince and Sine (1999)?Acetylcholine and epibatidine binding to muscle acetylcholine receptors distinguish between concerted and uncoupled models; J. Biol. Chem.,?274?19623
5) Sakust and Yoneda (1994)?Inhibition by SKF 525A and quinacrine of endogenous glibenclamide-sensitive K+ channels in follicle-enclosed Xenopus oocytes; Eur. J. Pharmacol.,?252?117
Check Digit Verification of cas no
The CAS Registry Mumber 62-68-0 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 6 and 2 respectively; the second part has 2 digits, 6 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 62-68:
(4*6)+(3*2)+(2*6)+(1*8)=50
50 % 10 = 0
So 62-68-0 is a valid CAS Registry Number.
InChI:InChI=1/C23H31NO2.ClH/c1-4-17-23(20-13-9-7-10-14-20,21-15-11-8-12-16-21)22(25)26-19-18-24(5-2)6-3;/h7-16H,4-6,17-19H2,1-3H3;1H
