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Many drugs have both a good side and a bad side

(August 13, 1998 00:30 a.m. EDT http://www.nandotimes.com) -- Hold the palm of
your left hand in front of a mirror. It reflects an image of your right hand.
Your right hand reflects an image of your left hand. Each foot also is a
mirror image of the other.

The same mirror image effect exists on an invisible scale in the molecules
that make up medicines and other chemical compounds. It is fostering a quiet
revolution in the design of safer, more effective drugs for millions of
patients.

A molecule of a drug is the smallest unit that can exist and still have the
drug's properties. Molecules are made from atoms of carbon, hydrogen, oxygen,
and other elements linked or bonded together in precise three-dimensional
architectures.

Drugs and other chemical compounds with the mirror image effect are called
"chiral" drugs. They exist in two molecular forms, usually termed the "D" or
right-handed form and the "S" or left-handed form.

The forms are termed enantiomers, or isomers. Each form is the mirror image of
the other, just like human hands and feet. Placed in front of a mirror, a
chiral molecule would reflect its mirror image, just like a right hand
reflects an image of a left hand.

Drugs that contain a mixture of the two isomers are called racemates, or
racemic mixtures. Scientists have been aware of the two-faced nature of chiral
molecules for 150 years.

Louis Pasteur, the famous French chemist and microbiologist, pioneered
research on the topic. But until recently, scientists paid little attention to
the common practice of selling drugs as racemic mixtures.

The last 15 years brought growing realization that each isomer in such a
mixture may have very different effects on the body. In some instances, one
isomer causes the medicine's beneficial effects. The other causes side
effects.

Thalidomide, the infamous birth defects drug of the 1960s, is an example.
Scientists now believe that only the "S" isomer causes birth defects when
taken by pregnant women.

Other examples of the two faces of mirror-image molecules abound. One isomer
of ibuprofen, the popular pain medicine, can cause side effects. One isomer of
the drug, albuterol, relaxes airways in thelung and helps asthma patients
breathe  easier. The other form constricts airways.

One isomer of the antibiotic, chloramphenicol, battles infections. The other
is inactive. One isomer of Ritalin combats attention deficit hyperactivity
disorder and the other may cause side effects.

Molecules in pesticides, fragrances, vitamins, and other products found in
everyday life also have the mirror-image effect. One isomer of a compound
called carvone has a spearmint flavor, for instance, while the other tastes
like caraway.

The U.S. Food and Drug Administration (FDA) has quietly taken steps to
encourage drug manufacturers to market more medications that consist of just
the beneficial isomer.

FDA's Fast Track Single Isomer (FTSI) Program, for instance, encourages drug
manufacturers to develop single-isomer versions of existing drugs. FTSI allows
marketing of single-isomer versions without all the costly testing required
for new drugs.

But the biggest impact has been on drugs still in the pharmaceutical industry
pipeline. An estimated 80 per cent of these are single-isomer versions, rather
than mixtures.

This quiet revolution promises many benefits for consumers. Single-isomer
drugs usually are safer, more effective, and faster-acting. The dose usually
is 50 per cent less than the dose of a racemic mixture.

Chirality matters in everyday life and in the world of molecules. An isomer
with no beneficial effect in a drug is as much a mismatch in medicine as a
shoe put on the wrong foot.

Michael Woods, Scripps Howard News Service
Copyright 1998 Nando.net
Copyright 1998 Scripps Howard

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