TAMPING DOWN NICOTINE'S IMAGE

NEW YORK---If a biographer wanted to wnte about about a spectacular comeback
from notoriety to respectability, and the tenuous nature of comebacks, a
good subject might be nicotine.

After denouncing nicotine for the highly addictive properties that hook
people on tobacco, scientists are rehabilitating it, not only as a means of
helping smokers to break their habit, but also as a potential treatment for
a variety of other disorders,.including stress, the intestinal condition
ulcerative colitis, Alzheimer's disease Parkinson's disease, attention
deficit disorder and Tourette ' s syndrome.

Nicotine-replacement products, developed to help people quit smoking, used
to consist only of chewing gum and skin patches, but now a nasal spray is
available by prescription, as well as a product called an inhaler, which is
really a fake cigarette made of plastic that a person sucks to g82t a dose
of menthol-flavored nicotine into the mouth and throat, but not the lungs.

In addition, doctors are awaiting the approval of a nicotine tablet that
patients will dissolve under their tongues to help fight their craving. In
all the products, the nicotine is extracted from tobacco leaves.

But just as nicotine approaches the edges of respectability, a few
researchers have begun to raise caution flags. Although all agree that
replacement nicotine is safer than smoking---and worth some risk if it helps
a person quit---a few are beginning to worry that some smokers are using
nicotine products not just for the short periods the products were designed
for, but for years.

They fear this use will only increase if nicotine products proliferate and
if more become available over the counter, as the patches and gum already
are. And if nicotine or drugs chemically related to it do come into use to
treat chronic diseases, the researchers say, there may be important side
effects to take into consideration.

Recent studies directed by Bianca Conti-Fine, a professor of biochemistry
and pharmacology at the University of Minnesota in Minneapolis-St. Paul,
suggest that nicotine can damage cells that line blood vessels and the
airways in the lungs. Papers by Dr. Conti-Fine and her colleagues were
published last month in the Journal of Pharmacology and Experimental
Therapeutics, and this month in Molecular Pharmacology.

The findings, which have raised concerns about the products among some other
researchers in the field, have led Dr. Conti-Fine to warn that nicotine
patches, gum and other similar products may not be safe if they are used
beyond the three to six months recommended for smoking cessation.

DR. Conti-Fine said, "If I were a smoker, I would certainiy take the
replacement for a while, but nat forever. Long-term usage might have the
potential to cause problems, and I think it should be looked at with great
caution. "

Her warning extended to proposals to use nicotine over a long term to treat
disorders like Alzheimer's disease and attention deficit disorder.

In studies of cells grown in the laboratory, she and her colleagues have
found that cells lining the blood vessels 85nd lungs carry nicotine
receptors, molecules on the cell surface that link up with nicotine, which
can then disrupt the cells. Normally, the receptors bind to a signaling
molecule, acetylcholine, which plays an essential role in stimulating the
cells to maintain their shape and connection to each other.

As Dr. Conti-Fine described it, the cells that line the lungs, blood vessels
and other surfaces in the body exist in a stretched and flattened shape and
butt up against one another like floor tiles. By activating its receptor,
acetylcholine directs the cells to stretch and flatten.

When nicotine parks at the receptor in acetylcholine's place, it initially
activates the receptor, but then causes it to stop working, a process called
desensitization. When that oc,curs; the signal to-stretch is broken, and the
cell balls up. "It rips off its connection with neighboring cells, and you
make a hole," Dr. ContiFine said.

In the blood vessels, she continued, those holes may result in lesions that
develop into artery disease. In the lungs, the holes may lead to bronchitis,
and in smokers the holes may help other, cancercausing chemicals in
cigarette smoke to penetrate the cells.

She said she was particularly concerned about "smokeless cigarettes," RJR
Nabisco's Eclipse and Philip Morris Cos.' Accord, which are being marketed
in some parts of the United States. The products release nicotine by heating
tobacco rather than burning it, and are marketed as safer than cigarettes
because they expose the lungs to far lower levels of tars and other
dangerous combustion products. But Dr. Conti-Fine said that if, as her
studies suggest, nicotine itself is harmful, then people who use the
smokeless products still risk lung disease.

Nicotine gum and patches do not expose the lungs to much nicotine, even from
the bloodstream, Dr. Conti-Fine said, so its damaging effects on the lungs
are unlikely to show up in people who use those products and do not smoke.
But the replacement products would expose the blood vessels to nicotine.
"This is very strong circumstantial evidence that nicotine would have a
direct, facilitating action on atherosclerosis," Dr. Conti-Fine said.

TO some researchers, the circumstantial nature of the evidence is a problem,
particularly because there is no evidence from studies in people that
nicotine gum or patches do any damage. And scientists have been on the
lookout for harmful effects, especially on the heart and arteries.

A large study published in 1996 found no ill effects from nicotine gum, even
among men who had used it regularly for five years. Another study showed no
health problems in men who wore three patches a day for several months,
three times the usual dose.

Checked-by: Don Beck