Norverapamil hydrochloride

Names

[ Name ]:
Norverapamil hydrochloride

[Synonym ]:
N-Nor-(+/-)-verapamil hydrochloride
Nor Verapamil Hydrochloride
Norverapamil hydrochloride
Norverapamil (hydrochloride)

Biological Activity

[Description]:

Norverapamil is a calcium channel blocker， it is the main active metabolite of verapamil.In vitro: Norverapamil is similarly effective as verapamil at inhibiting isoniazid and rifampicin tolerance and killing of intracellular M. tuberculosis in the absence of other drugs. norverapamil, also inhibits macrophage-induced tolerance and achieves similar serum levels to verapamil.[1] Norverapamil (NOR) is the major metabolite and shows approximately 20% of the efficacy of VER with regard to the vasodilation effect, but shows no antiarrhythmic activity. [2] Verapamil and its major metabolite norverapamil were identified to be both mechanism-based inhibitors and substrates of CYP3A and reported to have non-linear pharmacokinetics in clinic. [3]

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> Calcium Channel

Research Areas >> Cardiovascular Disease

[References]

[1]. Adams KN et al. Verapamil, and its metabolite norverapamil, inhibit macrophage-induced, bacterial efflux pump-mediated tolerance to multiple anti-tubercular drugs. J Infect Dis. 2014 Aug 1;210(3):456-66.

[2]. Singhal P et al. Enantiomeric separation of verapamil and its active metabolite, norverapamil, and simultaneous quantification in human plasma by LC-ESI-MS-MS. J Chromatogr Sci. 2012 Oct;50(9):839-48.

[3]. Wang J et al. A semi-physiologically-based pharmacokinetic model characterizing mechanism-based auto-inhibition to predict stereoselective pharmacokinetics of verapamil and its metabolite norverapamil in human. Eur J Pharm Sci. 2013 Nov 20;50(3-4):290-302.

[Related Small Molecules]

Chemical & Physical Properties

[ Melting Point ]:
155-160â„ƒ dec.

[ Molecular Formula ]:
C₂₆H₃₇ClN₂O₄

[ Molecular Weight ]:
477.04

[ LogP ]:
2.02400

[ Storage condition ]:
2-8℃

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H315-H319-H335

[ Precautionary Statements ]:
P301 + P312 + P330-P305 + P351 + P338

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
UN 2811 6.1/PG 3

Articles

Verapamil, and its metabolite norverapamil, inhibit macrophage-induced, bacterial efflux pump-mediated tolerance to multiple anti-tubercular drugs.

J. Infect. Dis. 210(3) , 456-66, (2014)

Drug tolerance likely represents an important barrier to tuberculosis treatment shortening. We previously implicated the Mycobacterium tuberculosis efflux pump Rv1258c as mediating macrophage-induced ...

Application of permeability-limited physiologically-based pharmacokinetic models: part II - prediction of P-glycoprotein mediated drug-drug interactions with digoxin.

J. Pharm. Sci. 102(9) , 3161-73, (2013)

Digoxin is the recommended substrate for assessment of P-glycoprotein (P-gp)-mediated drug-drug interactions (DDIs) in vivo. The overall aim of our study was to investigate the inhibitory potential of...

Stereoselective CZE method for analysis of verapamil and norverapamil in human plasma.

Acta Pol. Pharm. 70(3) , 395-401, (2013)

A stereospecific capillary zone electrophoresis (CZE) method was developed for the determination of verapamil (VER) and its main metabolite norverapamil (NOR) in human plasma. Optimal temperature, cyc...