Pharmaceutical companies have until now failed to produce the anti-obesity drug needed by millions of Europeans and Americans.

Only two other drugs are currently on the market approved for long-treatment of obesity. They are the lipase inhibitor orlistat, the leading medicine for weight reduction, and sibutramine. Use of both products has been limited by side effects.

But two other diet drugs that like Acomplia interact with the CB-1 receptor are now in Phase III trials, suggesting that there may be several new diet drugs on the market in the next few years.

Merck & Co. is developing a diet drug, Taranabant, that is a CB-1 receptor inverse agonist, and is hoping to file for U.S. Food and Drug Administration approval of its weight loss drug in 2008.

Pfizer also has a CB-1 receptor antagonist, known only as CP-945598, in Phase III trials, but has not yet announced when it expects to file for FDA approval.

During the past few years, the only other anti-obesity drug that made it as far as Phase III trials was Axokine. But the results for Axokine were ultimately very discouraging.

A drug that is currentlly widely prescribed for epilepsy, Topamax, has shown promise in both helping people lose weight and in keeping the weight off, but clinical trials of its use in promoting weight loss had to be discontinued because of side effects, primarily involving the central nervous system.

Another anti-obesity drug viewed as promising, ATL-962, which blocks fat absorption, may make it into Phase III clinical trials this year.

A profile of major anti-obesity drugs already on the market follows:

Xenical

Approved by the U.S. FDA in 1999, Xenical^® (orlistat) is a lipase inhibitor for obesity management that acts by inhibiting the absorption of dietary fats. Xenical prevents enzymes in the gastrointestinal tract from breaking down dietary fats into smaller molecules that can be absorbed by the body. This undigested fat is removed in your bowel movements, and absorption of fat is decreased by about 30 percent.

The recommended dose of Xenical is one capsule with each main meal that includes fat. During treatment, the patient should be on a nutritionally balanced, reduced-calorie diet that contains no more than 30 percent of calories from fat. Xenical is indicated for obese patients with a body mass index of 30 or more, or for patients with a BMI of 27 or more who also have high blood pressure, high cholesterol, or diabetes.

The most common side effects of Xenical are oily spotting, gas with discharge, fecal urgency, fatty/oily stools and frequent bowel movements.

Meridia

Approved by the U.S. FDA in 1997, Meridia^® (sibutramine) is thought to decrease your appetiite by inhibiting the reuptake of serotonin, norepinephrine, and dopamine in the brain.

By doing this, Meridia helps increase the levels of these hormones that control appetite and hunger. It was the first selective serotonin reuptake inhibitor (SSRI) to be used specifically for weight loss, although other drugs in the same class (Prozac, Paxil) have been used as anti-depressants.

Sibutramine (which is marketed as Reductil in Europe) is indicated for obese patients with a body mass index of 30 or more, or for patients with a BMI of 27 or more who also have high blood pressure, high cholesterol, or diabetes.

The drug causes a small increase in average blood pressure, and causes a higher increase in some patients.

Phentermine

First approved almost half a century ago in 1959 as an appetite suppressant, phentermine is sold under a variety of brand names including Ionamin and Adipex-P as well as under its generic name.

Phentermine is a sympathomimetic amine, which is similar to an amphetamine. It is also known as an "anorectic" or "anorexigenic" drug. It stimulates the central nervous system (nerves and brain), which increases your heart rate and blood pressure, and it suppresses your appetite.

During the 1990s, Phentermine was commonly used with another medication called Fenfluramine hydrochloride in a combination referred to as Fen-phen.

In 1997, this combination became the center of a storm, and fenfluramine and dexfenfluramine were taken off the market for possibly causing heart valve damage.

Because of possible adverse effects and contraindications for use, Phentermine is generally used to treat obesity only for a brief period of time.