Chemical Structure of Alprostadil

First isolated in 1957 from sheep prostate glands, Alprostadil is now known to occur naturally in many tissues of the human body. Synthetic Alprostadil has found use as a medication as well, useful for a variety of purposes because it causes the widening of blood vessels.

Alprostadil as a Medication

• Alprostadil's primary medical effect is relaxing the blood vessels.

  Alprostadil is best known as a treatment for erectile dysfunction, and it has also been investigated for use in female sexual arousal disorder. It is less well-known that alprostadil has long been used therapeutically in infants with congenital heart disease. All of Alprostadil's current medical applications arise from its ability to relax smooth muscle and cause vasodilation, or widening of the blood vessels.

The Prostaglandins

• Like siblings, members of the prostaglandin family share certain traits--but they can act very differently.

  Alprostadil is the trade name for prostaglandin E1, just one prostaglandin in a family of lipid-based (fatty) molecules. The prostaglandins have a broad spectrum of biological effects on the cardiovascular system, smooth muscle and the blood, but they all share a structural family resemblance: a five-membered ring trailing two carbon chains or "tails." Each prostaglandin is composed of a modified 20-carbon chain.

Alprostadil's Structural Features

• Alprostadil's five-membered ring is often depicted as a pentagon with a carbon at each point.

  Alprostadil's five-carbon ring is decorated with one hydroxyl group (an oxygen with a pendant hydrogen) and one carboxyl group (an oxygen double-bonded to the ring). These two groups are located on different carbon atoms, with one unfunctionalized carbon between them. The ring carbon on the other side of the hydroxyl group is attached to the "alkyl" tail, which has eight member carbons with a double bond between the two carbons nearest the ring and another hydroxy group off of the third carbon from the ring. Alprostadil's other tail, attached to the carbon on the other side of the hydroxyl group, is seven carbons long and has an acid group located at its terminus. Other prostaglandins sport different functional groups and different distributions of double bonds, which imbue them with their diverse biological activities.

Why is Structure Important?

• Small structural changes can produce opposite effects.

  There are at least nine known prostaglandin receptors that recognize molecules in this family and cause physiological reactions in response. Alprostadil's structure is what allows it to fit, like a key in a lock, into certain prostaglandin receptors and produce the vasodilation that is its primary medical effect. Other prostaglandins, only subtly different in structure, can bind to other receptors to produce vasoconstriction--the opposite effect.

Alprostadil in the Body

• Alprostadil has a short lifetime in the body.

  Like other prostaglandins, Alprostadil is synthesized enzymatically in the body from the essential fatty acid derivative arachidonic acid. Its physiological lifetime is short, taking only 5 to 15 minutes for 50 percent of it to degrade, because the hydroxyl group on the alkyl tail, essential to its receptor binding properties, is very susceptible to oxidation. For this reason, Alprostadil for erectile dysfunction is injected locally into the penis rather than taken as a pill. When used systemically, it must be infused continuously to maintain its effect.