Verapamil hydrochloride Chemical Properties

Melting point:

142 °C (dec.)(lit.)

storage temp. 

0-6°C

solubility 

methanol: 50 mg/mL, clear, colorless

form 

powder

color 

white

BCS Class

1,2

CAS DataBase Reference

23313-68-0(CAS DataBase Reference)

Safety Information

Hazard Codes 

T,Xi

Risk Statements 

23/24/25-36/37/38

Safety Statements 

36/37-45-37/39-26

RIDADR 

UN 2811 6.1/PG 3

WGK Germany 

3

RTECS 

YV8320000

F 

8-10

MSDS

• Language:English Provider:ACROS
• Language:English Provider:SigmaAldrich

Verapamil hydrochloride Usage And Synthesis

Description

Verapamil hydrochloride (VRP) is a phenylalkylamine calcium ion influx inhibitor (calcium antagonist). Verapamil hydrochloride exerts its pharmacologic effects by modulating the influx of ionic through the slow channels of vascular smooth muscle and cardiac cell membranes. It is widely used for the treatment of hypertension, angina pectoris, supraventricular tachycardia, myocardial infraction, and vascular headaches. Verapamil has also been used in cell biology as an inhibitor of drug efflux pump proteins such as P-glycoprotein, which are often over-expressed in certain tumor cell lines The plasma half-life of verapamil hydrochloride is 2–7 hours, which necessitates multiple dosing. After oral administration of VRP to humans, the drug is rapidly absorbed and widely distributed. It is approximately 90% absorbed from the gastrointestinal tract but is subject to considerable first pass metabolism and its bioavailability is around 20–30%. The low bioavailability is owing to the rapid biotransformation in the liver with a biological half-life of 4.0±1.5 hours.

References

[1] https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3bee2d26-138c-4641-a217-a38d3d657461
[2] V. Kusum Devi, S. Saisivam, G. R. Maria, P. U. Deepti (2003) Design and Evaluation of Matrix Diffusion Controlled Transdermal Patches of Verapamil Hydrochloride, 29, 495-503.
[3] https://www.caymanchem.com/product/14288
[4] Yuveraj Singh Tanwar, Pushpendra Singh Naruka, Garima Rani Ojha (2007) Development and evaluation of floating microspheres of verapamil hydrochloride, 43, 529-534

Chemical Properties

White Powder

Uses

A calcium channel blocker. Antihypertensive; antianginal; antiarrhythmic (class IV)

Uses

Calcium antagonists

brand name

Calan (Searle); Covera (Searle); Isoptin (FSC); Isoptin (Par); Verelan (Elan).

Clinical Use

Calcium-channel blocker:
Supraventricular arrhythmias
Angina
Hypertension
Cluster headaches (unlicensed)

Veterinary Drugs and Treatments

Veterinary experience with this agent is somewhat limited, but in dogs and cats verapamil may be useful for supraventricular tachycardias and, possibly, treatment of atrial flutter or fibrillation.

Drug interactions

Potentially hazardous interactions with other drugs
Aminophylline and theophylline: enhanced effect of aminophylline and theophylline.
Anaesthetics: increased hypotensive effect.
Anti-arrhythmics: increased risk of amiodaroneinduced bradycardia, AV block and myocardial depression; increased risk of myocardial depression and asystole with disopyramide and flecainide; increased risk of bradycardia and myocardial depression with dronedarone.
Antibacterials: metabolism increased by rifampicin; metabolism possibly inhibited by erythromycin, clarithromycin and telithromycin (increased risk of toxicity).
Anticoagulants: possibly increases dabigatran concentration - reduce dabigatran dose.
Antidepressants: enhanced hypotensive effect with MAOIs; concentration of imipramine and possibly other trycyclics increased; concentration significantly reduced by St John’s wort.
Antiepileptics: effect probably reduced by barbiturates, phenytoin and primidone; enhanced effect of carbamazepine.
Antifungals: negative inotropic effect possibly increased with itraconazole.
Antihypertensives: enhanced hypotensive effect, increased risk of first dose hypotensive effect of postsynaptic alpha-blockers.
Antipsychotics: possibly increases concentration of lurasidone.
Antivirals: concentration possibly increased by atazanavir and ritonavir; use telaprevir with caution.
Avanafil: concentration of avanafil increased.
Beta-blockers: enhanced hypotensive effect; risk of asystole, severe hypotension and heart failure if coprescribed with beta-blockers.
Cardiac glycosides: increased levels of digoxin. Increased AV block and bradycardia.
Ciclosporin: variable reports of decreased nephrotoxicity and potentiated effect; may also increase ciclosporin levels.
Colchicine: possibly increased risk of colchicine toxicity - suspend or reduce colchicine, avoid concomitant use in renal or hepatic failure.
Cytotoxics: possibly increased bosutinib, doxorubicin, ibrutinib concentration - reduce dose of bosutinib and ibrutinib; possibly increased risk of bradycardia with crizotinib; concentration of both drugs may be increased in combination with everolimus - consider reducing everolimus dose; concentration of olaparib possibly increased - avoid or reduce olaparib dose.
Fingolimod: increased risk of bradycardia.
Grapefruit juice: concentration increased - avoid concomitant use.
Ivabradine: concentration of ivabradine increased - avoid concomitant use.
Lenalidomide: possibly increases lenalidomide concentration.
Lipid-lowering agents: increased myopathy with atorvastatin and simvastatin - reduce dose of atorvastatin, do not exceed 20 mg of simvastatin1 , concentration of verapamil increased by atorvastatin; concentration of lomitapide increased - avoid.
Sirolimus: concentration of both drugs increased.
Tacrolimus: may increase tacrolimus levels.

Metabolism

Verapamil undergoes considerable first pass loss and is extensively metabolised in the liver. 12 metabolites have been identified. Of these only norverapamil has any significant activity (approximately 20
% that of the parent compound). Norverapamil represents about 6
% of the dose eliminated in urine and reaches steady-state plasma concentrations approximately equal to those of verapamil. About 70
% of a dose is excreted by the kidneys in the form of its metabolites but about 16
% is excreted in the bile into the faeces. Less than 4
% is excreted unchanged.

Purification Methods

The salt is purified by dissolving it in EtOH, filtering (if insoluble particles are present) and adding Et2O, filtering the salt, washing it with Et2O and drying it in vacuo. It has the following solubilities: hexane (0.001%), CH2Cl2 (~10%), MeOH (~10%), EtOH (20%) and H2O (8.3%). It has UV max at 232 and 278nm. The free base is a viscous yellow oil b 243-246o/0.01mm (n 25D 1.5448) and is almost insoluble in H2O but soluble in organic solvents. It is a Ca channel antagonist and is a coronary vasodilator. [Ramuz Helv Chim Acta 58 2050 1975, Harvey et al. Biochem J 257 95 1989.]

Verapamil hydrochloride(23313-68-0)Related Product Information

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