Prenylamine

Prenylamine

Clinical data
Routes of administration	Oral
ATC code	C01DX02 (WHO)
Legal status
Legal status	Uncontrolled
Identifiers
IUPAC name (RS)-N-(1-methyl-2-phenylethyl)-3,3-diphenylpropan-1-amine
Synonyms	N-(3,3-diphenylpropyl)amphetamine
CAS Number	390-64-7
PubChem (CID)	9801
ChemSpider	9418
UNII	K2OH82Z000
ChEMBL	CHEMBL24072
ECHA InfoCard	100.006.246
Chemical and physical data
Formula	C24H27N
Molar mass	329.48 g/mol
3D model (Jmol)	Interactive image
SMILES CC(Cc1ccccc1)NCCC(c2ccccc2)c3ccccc3
InChI InChI=1S/C24H27N/c1-20(19-21-11-5-2-6-12-21)25-18-17-24(22-13-7-3-8-14-22)23-15-9-4-10-16-23/h2-16,20,24-25H,17-19H2,1H3 Key:IFFPICMESYHZPQ-UHFFFAOYSA-N
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Prenylamine (Segontin) is a calcium channel blocker of the amphetamine chemical class which was used as a vasodilator in the treatment of angina pectoris; it was introduced in the 1960s by German manufacturer Albert-Roussel pharma gmbh^[1][2] which was acquired by Hoechst AG in 1974 and which in turn became part of Sanofi Aventis in 2005.

It was withdrawn from market worldwide in 1988 because it caused QT prolongation and Torsades de pointes which in turn caused sudden death.^[1][3]

The cardiac side effects were not detected during clinical development, but only emerged after the drug was widely used.^[1]

Prenylamine has two primary molecular target in human, Calmodulin and Myosin light-chain kinase 2 found in skeletal and cardiac muscle.^[4] Pharmacologically, it decreases the sympathetic stimulation on cardiac muscle predominantly through partial depletion of catecholamine via competitive inhibition of reuptake by storage granule, which lead to further depletion due to spontaneous leakage as a result of disturbance of equilibrium.^[5] 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.^[6] 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.^[5]

References

1. Shah, Rashmi R. (2007). "Withdrawal of Terodiline: A Tale of Two Toxicities". In Mann, Ronald D.; Andrews, Elizabeth B. Pharmacovigilance (2nd ed. ed.). Chichester, England: John Wiley & Sons. p. 116. ISBN 9780470059227.
2. 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.
3. 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.
4. DrugBank, ed. (2016-08-17). "Prenylamine". DrugBank.
5. 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.
6. 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.