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Trade namesIsoptin, Calan, others[1]
  • (RS)-2-(3,4-Dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl]-(methyl)amino}-2-prop-2-ylpentanenitrile
Clinical data
Drug classCalcium channel blocker
  • AU: C[2]
  • US: C (Risk not ruled out)[2]
Routes of
By mouth, intravenous
Defined daily dose0.24 gram (by mouth)
0.24 (parenteral)[3]
External links
License data
Legal status
  • UK: POM (Prescription only) [4]
  • US: ℞-only
  • In general: ℞ (Prescription only)
Elimination half-life4-6 hours[5]
Excretionkidney: 11%
Chemical and physical data
Molar mass454.611 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • N#CC(c1cc(OC)c(OC)cc1)(CCCN(CCc2ccc(OC)c(OC)c2)C)C(C)C
  • InChI=1S/C27H38N2O4/c1-20(2)27(19-28,22-10-12-24(31-5)26(18-22)33-7)14-8-15-29(3)16-13-21-9-11-23(30-4)25(17-21)32-6/h9-12,17-18,20H,8,13-16H2,1-7H3 checkY

Verapamil, sold under various trade names,[1] is a medication used for the treatment of high blood pressure, angina (chest pain from not enough blood flow to the heart), and supraventricular tachycardia.[6] It may also be used for the prevention of migraines and cluster headaches.[7][8] It is given by mouth or by injection into a vein.[6]

Common side effects include headache, low blood pressure, nausea, and constipation.[6] Other side effects include allergic reactions and muscle pains.[9] It is not recommended in people with a slow heart rate or heart failure.[9] It is believed to cause problems for the baby if used during pregnancy.[2] It is in the non–dihydropyridine calcium channel blocker family of medications.[6]

Verapamil was approved for medical use in the United States in 1981.[6][10] It is on the World Health Organization's List of Essential Medicines.[11] Verapamil is available as a generic medication.[6] The wholesale cost in the developing world is about US$1.71–2.70 per month.[12] In the United States a month of treatment costs $25–50.[13] Long acting formulations exist.[9] In 2017, it was the 145th most commonly prescribed medication in the United States, with more than four million prescriptions.[14][15]

Medical uses

Verapamil (brand name Verelan) 300-mg extended-release capsule

Verapamil is used for controlling ventricular rate in supraventricular tachycardia and migraine headache prevention.[16] It is a class-IV antiarrhythmic and more effective than digoxin in controlling ventricular rate.[17] Verapamil is not listed as a first line agent by the guidelines provided by JAMA in JNC-8.[18] However, it may be used to treat hypertension if patient has co-morbid atrial fibrillation or other types of arrhythmia.[19][20]

Verapamil is also used intra-arterially to treat cerebral vasospasm.[21] Verapamil is used to treat the condition cluster headache.[22] Tentative evidence supports the use of verapamil topically to treat plantar fibromatosis.[23]


The defined daily dose is 0.24 gram (by mouth) or 0.24 mg (parenteral)[3]


Use of verapamil is generally avoided in people with severe left ventricular dysfunction, hypotension (systolic blood pressure less than 90 mm Hg), cardiogenic shock, and hypersensitivity to verapamil.[24] It is also contraindicated in people with atrial flutter or fibrillation and an existing accessory tract such as in Wolff-Parkinson-White syndrome.[25][24]

Side effects

The most common side effect of verapamil is constipation (7.3%). Other side effects include dizziness (3.3%), nausea (2.7%), low blood pressure (2.5%), and headache 2.2%. Other side effects seen in less than 2% of the population include: edema, congestive heart failure, pulmonary edema, fatigue, elevated liver enzymes, shortness of breath, low heart rate, atrioventricular block, rash and flushing.[24] Along with other calcium channel blockers, verapamil is known to induce gingival enlargement.[26]


Acute overdose is often manifested by nausea, weakness, slow heart rate, dizziness, low blood pressure, and abnormal heart rhythms. Plasma, serum, or blood concentrations of verapamil and norverapamil, its major active metabolite, may be measured to confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities. Blood or plasma verapamil concentrations are usually in a range of 50–500 μg/l in persons on therapy with the drug, but may rise to 1–4 mg/l in acute overdose patients and are often at levels of 5–10 mg/l in fatal poisonings.[27][28]

Mechanism of action

Verapamil's mechanism in all cases is to block voltage-dependent calcium channels.[24] In cardiac pharmacology, calcium channel blockers are considered class-IV antiarrhythmic agents. Since calcium channels are especially concentrated in the sinoatrial and atrioventricular nodes, these agents can be used to decrease impulse conduction through the AV node, thus protecting the ventricles from atrial tachyarrhythmias. Verapamil is also a Kv voltage gated potassium channel blocker.[29]

Calcium channels are also present in the smooth muscle lining blood vessels. By relaxing the tone of this smooth muscle, calcium channel blockers dilate the blood vessels. This has led to their use in treating high blood pressure and angina pectoris. The pain of angina is caused by a deficit in oxygen supply to the heart. Calcium channel blockers like verapamil dilate blood vessels, which increases the supply of blood and oxygen to the heart.[24]

Cluster headaches

Preventive therapy with verapamil is believed to work because it has an effect on the circadian rhythm and on CGRPs. As CGRP-release is controlled by voltage-gated calcium channels.[30]

Pharmacokinetic details

More than 90% of verapamil is absorbed when given orally,[24] but due to high first-pass metabolism, bioavailability is much lower (10–35%). It is 90% bound to plasma proteins and has a volume of distribution of 3–5 l/kg. It takes 1 to 2 hours to reach peak plasma concentration after oral administration.[24] It is metabolized in the liver to at least 12 inactive metabolites (though one metabolite, norverapamil, retains 20% of the vasodilatory activity of the parent drug). As its metabolites, 70% is excreted in the urine and 16% in feces; 3–4% is excreted unchanged in urine. This is a nonlinear dependence between plasma concentration and dosage. Onset of action is 1–2 hours after oral dosage.

Half-life is 4–6 hours.[5]

It is not cleared by hemodialysis. It is excreted in human milk. Because of the potential for adverse reaction in nursing infants, nursing should be discontinued while verapamil is administered.[medical citation needed]

Verapamil has been reported to be effective in both short-term[31] and long-term treatment of mania and hypomania.[32] Addition of magnesium oxide to the verapamil treatment protocol enhances the antimanic effect.[33]

Veterinary use

Intra-abdominal adhesions are common in rabbits following surgery. Verapamil can be given postoperatively in rabbits which have suffered trauma to abdominal organs to prevent formation of these adhesions.[34][35][36] Such effect was not documented in another study with ponies.[37]


Diagram of proposed mechanisms of verapamil, mediating the proliferation, and protection of pancreatic β-cells[38]

Verapamil inhibits the ATP-binding cassette (ABC) transporter family of proteins found in stem cells and has been used to study cancer stem cells (CSC) within head and neck squamous cell carcinomas.[39]

Verapamil is also used in cell biology as an inhibitor of drug efflux pump proteins such as P-glycoprotein and other ABC transporter proteins.[40][39]

This is useful, as many tumor cell lines overexpress drug efflux pumps, limiting the effectiveness of cytotoxic drugs or fluorescent tags. It is also used in fluorescent cell sorting for DNA content, as it blocks efflux of a variety of DNA-binding fluorophores such as Hoechst 33342. Radioactively labelled verapamil and positron emission tomography can be used with to measure P-glycoprotein function.[medical citation needed]

Society and culture


The wholesale cost in the developing world is about US$1.71–2.70 per month.[12] In the United States a month of treatment costs $25–50.[13] In 2017, it was the 145th most commonly prescribed medication in the United States, with more than four million prescriptions.[14][15]

See also


  1. 1.0 1.1 "Verapamil". Archived from the original on 1 August 2017. Retrieved 14 December 2016.
  2. 2.0 2.1 2.2 "Verapamil Use During Pregnancy". 18 November 2019. Archived from the original on 21 December 2016. Retrieved 26 March 2020.
  3. 3.0 3.1 "WHOCC - ATC/DDD Index". Archived from the original on 29 October 2020. Retrieved 20 September 2020.
  4. "Securon SR - Summary of Product Characteristics (SmPC)". (emc). 17 May 2017. Archived from the original on 26 March 2020. Retrieved 26 March 2020.
  5. 5.0 5.1 Benowitz, Neal L. (2020). "11. Antihypertensive agents". In Katzung, Bertram G.; Trevor, Anthony J. (eds.). Basic and Clinical Pharmacology (15th ed.). New York: McGraw-Hill. p. 183. ISBN 978-1-260-45231-0. Archived from the original on 10 October 2021. Retrieved 5 December 2021.
  6. 6.0 6.1 6.2 6.3 6.4 6.5 "Verapamil Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  7. Tfelt-Hansen PC, Jensen RH (July 2012). "Management of cluster headache". CNS Drugs. 26 (7): 571–80. doi:10.2165/11632850-000000000-00000. PMID 22650381.
  8. Merison K, Jacobs H (November 2016). "Diagnosis and Treatment of Childhood Migraine". Current Treatment Options in Neurology. 18 (11): 48. doi:10.1007/s11940-016-0431-4. PMID 27704257.
  9. 9.0 9.1 9.2 World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. hdl:10665/44053. ISBN 9789241547659.
  10. "Isoptin: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 26 March 2020. Retrieved 26 March 2020.
  11. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  12. 12.0 12.1 "Verapamil HCL". International Drug Price Indicator Guide. Archived from the original on 22 January 2018. Retrieved 8 December 2016.
  13. 13.0 13.1 Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 156. ISBN 9781284057560.
  14. 14.0 14.1 "The Top 300 of 2020". ClinCalc. Archived from the original on 18 March 2020. Retrieved 11 April 2020.
  15. 15.0 15.1 "Verapamil Hydrochloride - Drug Usage Statistics". ClinCalc. Archived from the original on 8 July 2020. Retrieved 11 April 2020.
  16. Koda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs 10th edition. USA: LWW. 2012. pp. 497, 1349. ISBN 978-1609137137.
  17. Srinivasan V, Sivaramakrishnan H, Karthikeyan B (2011). "Detection, isolation and characterization of principal synthetic route indicative impurities in verapamil hydrochloride". Scientia Pharmaceutica. 79 (3): 555–68. doi:10.3797/scipharm.1101-19. PMC 3163365. PMID 21886903.
  18. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. (February 2014). "2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8)". JAMA. 311 (5): 507–20. doi:10.1001/jama.2013.284427. PMID 24352797.
  19. Koda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs. LWW; Tenth, North American edition. 2012. pp. 320–22. ISBN 978-1609137137.
  20. Beck E, Sieber WJ, Trejo R (February 2005). "Management of cluster headache". American Family Physician. 71 (4): 717–24. PMID 15742909. Archived from the original on 13 November 2015. Retrieved 4 November 2015.
  21. Jun P, Ko NU, English JD, Dowd CF, Halbach VV, Higashida RT, et al. (November 2010). "Endovascular treatment of medically refractory cerebral vasospasm following aneurysmal subarachnoid hemorrhage". AJNR. American Journal of Neuroradiology. 31 (10): 1911–6. doi:10.3174/ajnr.A2183. PMC 4067264. PMID 20616179.
  22. Drislane, Frank; Benatar, Michael; Chang, Bernard S.; Acosta, Juan; Tarulli, Andrew (1 January 2009). Blueprints Neurology. Lippincott Williams & Wilkins. pp. 71–. ISBN 978-0-7817-9685-9. Archived from the original on 8 June 2013. Retrieved 14 November 2010.
  23. Young, Joseph R; Sternbach, Sarah; Willinger, Max; Hutchinson, Ian D; Rosenbaum, Andrew J (17 December 2018). "The etiology, evaluation, and management of plantar fibromatosis". Orthopedic Research and Reviews. 11: 1–7. doi:10.2147/ORR.S154289. ISSN 1179-1462. PMC 6367723. PMID 30774465.
  24. 24.0 24.1 24.2 24.3 24.4 24.5 24.6 "Calan- verapamil hydrochloride tablet, film coated". DailyMed. 17 December 2019. Archived from the original on 26 March 2020. Retrieved 26 March 2020.
  25. "Securon 2.5 mg/ml IV Intravenous Injection - Summary of Product Characteristics (SmPC)". (emc). 24 November 2016. Archived from the original on 26 March 2020. Retrieved 26 March 2020.
  26. Steele RM, Schuna AA, Schreiber RT (April 1994). "Calcium antagonist-induced gingival hyperplasia". Annals of Internal Medicine. 120 (8): 663–4. doi:10.7326/0003-4819-120-8-199404150-00006. PMID 8135450.
  27. Wilimowska J, Piekoszewski W, Krzyanowska-Kierepka E, Florek E (2006). "Monitoring of verapamil enantiomers concentration in overdose". Clinical Toxicology. 44 (2): 169–71. doi:10.1080/15563650500514541. PMID 16615674.
  28. Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, California: Biomedical Publications. pp. 1637–39.
  29. Wang SP, Wang JA, Luo RH, Cui WY, Wang H (September 2008). "Potassium channel currents in rat mesenchymal stem cells and their possible roles in cell proliferation". Clinical and Experimental Pharmacology & Physiology. 35 (9): 1077–84. doi:10.1111/j.1440-1681.2008.04964.x. PMID 18505444.
  30. Petersen AS, Barloese MCJ, Snoer A, Soerensen AMS, Jensen RH (2019). "Verapamil and Cluster Headache: Still a Mystery. A Narrative Review of Efficacy, Mechanisms and Perspectives". Headache. 59 (8): 1198–1211. doi:10.1111/head.13603. PMID 31339562.{{cite journal}}: CS1 maint: uses authors parameter (link)
  31. Giannini AJ, Houser WL, Loiselle RH, Giannini MC, Price WA (December 1984). "Antimanic effects of verapamil". The American Journal of Psychiatry. 141 (12): 1602–3. doi:10.1176/ajp.141.12.1602. PMID 6439057.
  32. Giannini AJ, Taraszewski R, Loiselle RH (December 1987). "Verapamil and lithium in maintenance therapy of manic patients". Journal of Clinical Pharmacology. 27 (12): 980–2. doi:10.1002/j.1552-4604.1987.tb05600.x. PMID 3325531.
  33. Giannini AJ, Nakoneczie AM, Melemis SM, Ventresco J, Condon M (February 2000). "Magnesium oxide augmentation of verapamil maintenance therapy in mania". Psychiatry Research. 93 (1): 83–7. doi:10.1016/S0165-1781(99)00116-X. PMID 10699232.
  34. Elferink JG, Deierkauf M (January 1984). "The effect of verapamil and other calcium antagonists on chemotaxis of polymorphonuclear leukocytes". Biochemical Pharmacology. 33 (1): 35–9. doi:10.1016/0006-2952(84)90367-8. PMID 6704142.
  35. Azzarone B, Krief P, Soria J, Boucheix C (December 1985). "Modulation of fibroblast-induced clot retraction by calcium channel blocking drugs and the monoclonal antibody ALB6". Journal of Cellular Physiology. 125 (3): 420–6. doi:10.1002/jcp.1041250309. PMID 3864783.
  36. Steinleitner A, Lambert H, Kazensky C, Sanchez I, Sueldo C (January 1990). "Reduction of primary postoperative adhesion formation under calcium channel blockade in the rabbit". The Journal of Surgical Research. 48 (1): 42–5. doi:10.1016/0022-4804(90)90143-P. PMID 2296179.
  37. Baxter GM, Jackman BR, Eades SC, Tyler DE (1993). "Failure of calcium channel blockade to prevent intra-abdominal adhesions in ponies". Veterinary Surgery. 22 (6): 496–500. doi:10.1111/j.1532-950X.1993.tb00427.x. PMID 8116206.
  38. Arefanian, Hossein; Koti, Lubaina; Sindhu, Sardar; Ahmad, Rasheed; Al Madhoun, Ashraf; Al-Mulla, Fahd (2023). "Verapamil chronicles: advances from cardiovascular to pancreatic β-cell protection". Frontiers in Pharmacology. 14: 1322148. doi:10.3389/fphar.2023.1322148. ISSN 1663-9812.
  39. 39.0 39.1 Song, Jun; Chang, Insoon; Chen, Zhuo; Kang, Mo; Wang, Cun-Yu (6 July 2010). "Characterization of Side Populations in HNSCC: Highly Invasive, Chemoresistant and Abnormal Wnt Signaling". PLOS ONE. 5 (7): e11456. Bibcode:2010PLoSO...511456S. doi:10.1371/journal.pone.0011456. ISSN 1932-6203. PMC 2897893. PMID 20625515.
  40. Bellamy WT (1996). "P-glycoproteins and multidrug resistance". Annual Review of Pharmacology and Toxicology. 36: 161–83. doi:10.1146/ PMID 8725386.

External links

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