Drotaverine

Drotaverine (INN, also known as drotaverin) is an antispasmodic drug, used to enhance cervical dilation during childbirth and to relieve smooth muscle spasms in gastrointestinal tract, urinary system, and gall bladder.[2][3][4][5]

Not to be confused with doravirine.
Drotaverine
Clinical data
Trade namesNo-Spa, Doverin
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral, intravenous, intramuscular
ATC code
Legal status
Legal status
  • OTC (tablets), Rx-only (solution for injection) (RU)[1]
Pharmacokinetic data
BioavailabilityHighly variable (~65%), peak at 45–60 min
Protein binding95–98%
MetabolismHepatic
Elimination half-life7–16 hours
Excretion>50% in urine and ~30% in bile[1]
Identifiers
IUPAC name
  • (Z)-1-(3,4-diethoxybenzylidene)-6,7-diethoxy-1,2,3,4-tetrahydroisoquinoline
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.110.916
Chemical and physical data
FormulaC24H31NO4
Molar mass397.515 g·mol−1
3D model (JSmol)
SMILES
  • O(c1ccc(cc1OCC)\C=C3\c2c(cc(OCC)c(OCC)c2)CCN3)CC
InChI
  • InChI=1S/C24H31NO4/c1-5-26-21-10-9-17(14-22(21)27-6-2)13-20-19-16-24(29-8-4)23(28-7-3)15-18(19)11-12-25-20/h9-10,13-16,25H,5-8,11-12H2,1-4H3/b20-13- Y
  • Key:OMFNSKIUKYOYRG-MOSHPQCFSA-N Y
 NY (what is this?)  (verify)

It is structurally related to papaverine, and is a selective inhibitor of phosphodiesterase-4, and has no anticholinergic effects.[6]

It is available in Asia, India,[7] Central and Eastern Europe under several brand names.[8] Most known brand is No-Spa by Hungarian plant Chinoin (owned by Sanofi).

Pharmacodynamics

Drotaverine hydrochloride has a spasmolytic, myotropic, vasodilation, hypotensive action.[5]

Drotaverine decreases active ionized calcium supply binding to smooth muscle cells due to inhibition of phosphoesterase and cAMP intracellular accumulation of adenosine monophosphate. It has an apparent and prolonged action on smooth muscles of internal organs and blood vessels and it moderately decreases arterial blood pressure, increases cardiac output (minute volume of heart), and have some antiarrhythmic potential.[5]

Drotaverine decreases vascular tone of cerebral blood vessels and increases blood-filling. Practically, Drotaverine does not influence the autonomic nervous system and does not penetrate into the central nervous system.[5]

Side effects

Possible side effects include: heating sensation, dizziness, headache (rarely), insomnia. May be observed: arrhythmia (rarely), hypotension, tachycardia, sweating, nausea.[5]

Overdose of Drotaverine potentially can cause atrioventricular (AV) block, cardiac arrest, paralysis of respiratory system.[5]

Counterfeits

In Israel the product is known under the brand name "No-Spa" by the general public[9] which did not receive a permit to be distributed by the health ministry,[10] however due to high demand local medical counterfeiters have managed to smuggle No-Spa tablets over the years.[10]

In 2008, the Israeli health organization warned consumers against counterfeit No-SPA pills after a smuggler had been arrested at the Ben Gurion Airport with several thousand pills.[11][12]

In 2011, Israeli patent and trademark office declined the use of the No-SPA.[9]

Risks

An article from 2013 described the effects from overdose (in a 19-year-old woman) as including vomiting, seizures and fatal cardiac toxicity.[13]

In 2016, the young Russian chess player Ivan Bukavshin died of a massive overdose (or poisoning) of the drug, which was initially thought to be a stroke; dose detected in his blood was 17 mg/kg.[14]

References
  1. "Инструкция по применению препарата Но-шпа // No-Spa (tablets) Full Prescribing Information". National Register of Drugs (in Russian). Chinoin Pharmaceutical and Chemical Works. pp. 3–8.
  2. Padubidri V, Anand E (2006). Title Textbook of Obstetrics. BI Publications Pvt Ltd. p. 283. ISBN 9788172252236.
  3. Singh KC, Jain P, Goel N, Saxena A (January 2004). "Drotaverine hydrochloride for augmentation of labor". International Journal of Gynaecology and Obstetrics. 84 (1): 17–22. doi:10.1016/s0020-7292(03)00276-5. PMID 14698825. S2CID 43824027.
  4. "DROTAVERINE: Uses, Side Effects and Medicines | Apollo Pharmacy". www.apollopharmacy.in. Retrieved 2022-05-24.
  5. "RUE Belmedpreparaty - pharmaceutical enterprise in the Republic of Belarus - DROTAVERINE HYDROCHLORIDE". RUE Belmedpreparaty - pharmaceutical enterprise in the Republic of Belarus. Archived from the original on 2022-08-17. Retrieved 2022-05-24.
  6. "The DrugBank database: Drotaverine". DrugBank Version 4.1. The Metabolomics Innovation Centre. Retrieved 9 August 2014.
  7. "Drotaverine Drug Information - Indications, Dosage, Side Effects and Precautions". Medindia. Retrieved 2022-05-24.
  8. Drotaverine - Drugs.com Drugs.com international listings for drotaverine Page accessed June 28, 2015
  9. NO-SPA (also pronounced as No-SHPA) trade mark registration decision 202248, Israeli patent and trade mark office, 11 July 2007
  10. Health Ministry: Fake drug had been smuggled NRG, 11 March 2009
  11. ניב, שי (2008-02-11). "חשש כי תרופה מזויפת בשם NO-SPA הוברחה לישראל ועשויה לגרום לסכנה בריאותית" [It is feared that a fake drug called NO-SPA has been smuggled into Israel and may cause a health hazard]. Globes (in Hebrew).
  12. Bader, H (11 February 2008). "משרד הבריאות מזהיר משימוש בתרופה לא מאושרת בשם: No-Spa" [The Ministry of Health warns against the use of an unapproved medicine called: No-Spa]. Israel National News (in Hebrew). Archived from the original on 10 March 2022.
  13. Drotaverine overdose (case report) Reactions Weekly, Volume 1481 (1), page 17.
  14. Silence, lack of will, indifference Archived 2016-12-18 at the Wayback Machine (Russian, Chess-News)
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.