Prenylamine

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Prenylamine
Prenylamine.svg
Clinical data
Routes of
administration
Oral
ATC code C01DX02 (WHO)
Legal status
Legal status
  • Uncontrolled
Identifiers
CAS Number 390-64-7 N
PubChem CID 9801
ChemSpider 9418 N
UNII K2OH82Z000 N
ChEMBL CHEMBL24072 N
Synonyms N-(3,3-diphenylpropyl)amphetamine
Chemical and physical data
Systematic (IUPAC) name: (RS)-N-(1-methyl-2-phenylethyl)-3,3-diphenylpropan-1-amine
3D model (Jmol) Interactive image
Formula C24H27N
Molar mass 329.48 g/mol
 NYesY (what is this?)  (verify)

Prenylamine (Segontin) is a calcium channel blocker of the amphetamine chemical class which is used as a vasodilator in the treatment of angina pectoris. It has been shown to partially metabolize to amphetamine and can cause false positives for it in drug tests.[1][2][3] Additionally, its use as a stimulant is prohibited by the World Anti-Doping Agency.[4] Prenylamine also appears to act as a vesicular monoamine transporter inhibitor, and has been demonstrated to deplete vesicular monoamine neurotransmitter stores similarly to reserpine.[5]

Medical use[edit]

Prenylamine is used to treat angina pectoris.[6]

Adverse effects[edit]

Common adverse effects include Long QT, torsade de pointe, mild sedation, headaches, dizziness, flushing, skin reaction, dyspepsia, gastric discomfort, vomiting, diarrhea, and increased liver enzymes.[7]

Prenylamine is contraindicated in serious hepatic or renal impairment, gross arrhythmia and presence of uncompensated heart failure. Long term therapy may result in hyphenation and should avoid in the first trimester of pregnancy.[6]

Pharmacology[edit]

Mechanism of Action:[edit]

Prenylamine has two primary molecular target in human,Calmodulin and Myosin light-chain kinase 2 found in skeletal and cardiac muscle.[8] Pharmacologically, it decreases the sympathetic stimulation on cardiac muscle predominantly through partial depletion of catecholamine via competitive inhibition of of reuptake by storage granule, which lead to further depletion due to spontaneous leakage as a result of disturbance of equilibrium. [6] This depletion mechanism is similar to reserpine because both agents target the same site on storage granule, however prenylamine shows a high affinity for cardiac tissue while reserpine is more selective toward brain tissue. [9] Prenylamine also slows cardiac metabolism via calcium transport delay by blockade of magnesium-dependent calcium transport ATPase. It also demonstrate a beta blocker-like activity that result in reduction of heart rate however shows opposing effect on tracheal tissue response. [6]

Pharmcokinetics[edit]

The onset of action when admistered orally is about 1 hour. It is metablized in the liver. The half-life when administered via IV is 14 hours and when administered orally is 7 hours The time to peak serum concentration is 60 to 90 minutes. It is excreted about 40% in urine and about 37% in feces.[6]:

For oral administration the lowest published toxic dose is reported for men as being 13mg/kg and for women as 50mg/kg.[10]:

History[edit]

Prenylamine was originally manufactured under trade name Segotin® by German manufacturer Albert-Roussel pharma gmbh which is acquired by Hoechst AG in 1974. Hoechst AG is now a subsidiary of Sanofi Aventis since 2005. The prenylamine entered U.S. market in 1966[11] primarily for the treatment of Angina pectoris, however it has been withdrawal from market since 1988 due to major cardiac safety concern such as QT prolongation and Torsades de pointes result in sudden death.[12]

References[edit]

  1. ^ Kraemer T, Roditis SK, Peters FT, Maurer HH (March 2003). "Amphetamine concentrations in human urine following single-dose administration of the calcium antagonist prenylamine-studies using fluorescence polarization immunoassay (FPIA) and GC-MS". Journal of Analytical Toxicology. 27 (2): 68–73. doi:10.1093/jat/27.2.68. PMID 12669999. 
  2. ^ Musshoff F (February 2000). "Illegal or legitimate use? Precursor compounds to amphetamine and methamphetamine". Drug Metabolism Reviews. 32 (1): 15–44. doi:10.1081/DMR-100100562. PMID 10711406. 
  3. ^ Cody JT (May 2002). "Precursor medications as a source of methamphetamine and/or amphetamine positive drug testing results". Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 44 (5): 435–50. doi:10.1097/00043764-200205000-00012. PMID 12024689. 
  4. ^ "S6. Stimulants | List of Prohibited Substances and Methods". English. Retrieved 2016-11-21. 
  5. ^ Bagchi SP (1990). "Antidopaminergic action of verapamil and several other drugs: inactivation of vesicular dopamine". Life Sciences. 46 (12): 857–63. doi:10.1016/0024-3205(90)90115-8. PMID 1969603. 
  6. ^ a b c d e Murphy, J. Eric (1973-03-01). "Drug Profile: Synadrin". Journal of International Medical Research. 1 (3): 204–209. doi:10.1177/030006057300100312. ISSN 0300-0605. 
  7. ^ Winsor, Travis; Bleifer, Kenneth; Cole, Seymour; Goldman, I. Ralph; Karpman, Harold; Oblath, Robert; Stone, Samuel (1971-07-01). "A double-blind, double cross-over trial of prenylamine in angina pectoris". American Heart Journal. 82 (1): 43–54. doi:10.1016/0002-8703(71)90160-8. 
  8. ^ DrugBank, ed. (2016-08-17). "Prenylamine". DrugBank. 
  9. ^ Obianwu, Hopé O. (1965-04-01). "The Effect of Prenylamine (Segontin®) on the Amine Levels of Brain, Heart and Adrenal Medulla in Rats". Acta Pharmacologica et Toxicologica. 23 (4): 383–390. doi:10.1111/j.1600-0773.1965.tb00362.x. ISSN 1600-0773. 
  10. ^ Chambers, Michael. "ChemIDplus - K2OH82Z000 - IFFPICMESYHZPQ-UHFFFAOYSA-N - Prenylamine [USAN:INN:BAN] - Similar structures search, synonyms, formulas, resource links, and other chemical information.". chem.nlm.nih.gov. Retrieved 2016-11-21. 
  11. ^ Godfraind, Theophile; Herman, Arnold G.; Wellens, Donald (2012). Calcium Entry Blockers in Cardiovascular and Cerebral Dysfunctions. Springer Science & Business Media. p. 40. ISBN 9400960336 – via google books. 
  12. ^ Fung, Man; Thornton, Anna; Mybeck, Kathy; Wu, Jasmanda Hsiao-hui; Hornbuckle, Ken; Muniz, Edmundo (2001-01-01). "Evaluation of the Characteristics of Safety Withdrawal of Prescription Drugs from Worldwide Pharmaceutical Markets-1960 to 1999*". Drug Information Journal. 35 (1): 293–317. doi:10.1177/009286150103500134. ISSN 2168-4790.