Prenylamine (Segontin) is a

calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

of the

amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

chemical class Chemical classification systems attempt to classify elements or compounds according to certain chemical functional or structural properties. Whereas the structural properties are largely intrinsic, functional properties and the derived classificat ...

that was used as a

vasodilator Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...

in the treatment of angina pectoris.

History

Prenylamine was introduced in the 1960s by German manufacturer Albert-Roussel pharma gmbh, 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 It was withdrawn from market worldwide in 1988 because it caused QT interval prolongation and torsades de pointes, greatly increasing the risk of

sudden death Sudden Death or Sudden death may refer to: Medical * Cardiac arrest, also known as sudden cardiac death, natural death from cardiac causes * Sudden cardiac death of athletes * Sudden infant death syndrome * Sudden unexpected death in epilepsy * ...

. The cardiac side effects were not detected during clinical development, only becoming apparent after the drug was in wide use.

Mechanism of action

Prenylamine has two primary molecular targets in humans:

calmodulin Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the bind ...

and myosin light-chain kinase 2, found in skeletal and cardiac muscle. Pharmacologically, it decreases sympathetic stimulation on cardiac muscle, predominantly through partial depletion of catecholamines via competitive inhibition of reuptake by storage granules, leading to further depletion due to spontaneous leakage as a result of disturbance of equilibrium. This depletion mechanism is similar to that of

reserpine Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces m ...

because both agents target the same site on the storage granule; however, prenylamine shows a high affinity for cardiac tissue, while reserpine is more selective toward brain tissue. Prenylamine slows cardiac metabolism via calcium transport delay by blockade of magnesium-dependent calcium transport

ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...

. It demonstrate beta blocker–like activity that results in reduction of heart rate but shows an opposing effect on tracheal tissue response.

References

{{Phenethylamines Vasodilators Substituted amphetamines Calcium channel blockers Norepinephrine-dopamine releasing agents