A Cigarette Chemical Packed With Helpful Effects?
By John Schwartz- Washington Post Staff Writer
Monday, November 9, 1998
Everyone knows that smoking is bad for you. But not every component of a
cigarette is harmful. Take nicotine, the chemical that makes smoking
satisfying -- and addictive.
Nicotine serves as a natural insecticide in tobacco leaves. But the drug
is relatively benign to humans in normal doses, especially when compared
with the thousands of toxins in tobacco smoke.
In fact, nicotine has a wide array of potentially beneficial effects. As
a result, today nicotine is being studied as a possible therapy for a
broad range of ailments that includes Alzheimer's and Parkinson's
diseases, schizophrenia, depression, adult attention deficit disorder,
Tourette's syndrome and ulcerative colitis.
A second wave of research, meanwhile, is aimed at developing drugs that
mimic nicotine's positive effects but don't produce its negative side
effects. (Nicotine not only can cause nausea and rapid heartbeat, it
actually tends to burn out the very receptors in the brain that it
excites, forcing the brain to create more receptors to keep up.)
"There is a tremendous growth of interest in the nicotine field," said
Jed Rose, a Duke University researcher who co-hosts an annual scientific
conference devoted to the drug. "There's been a virtual explosion of new
findings on every level."
This trend was on display yesterday, when several groups of researchers
presented their latest work on nicotine and nicotine-like drugs at the
annual Society for Neuroscience conference in Los Angeles. The
presentations even included work by scientists at R.J. Reynolds Tobacco
Co. on a drug designed to mimic nicotine's ability to improve memory and
learning.
Research on nicotine as a possible treatment for disease got its start a
decade ago, as researchers began to notice that smokers suffered less
from certain diseases.
Nicotine, however, is not selective. It has many different, often
contradictory, effects on the body -- for example, it simultaneously
calms smokers and speeds up their heartbeat.
"It's just what we would call a 'dirty drug,' " said Phyllis C. Pugh, a
nicotine researcher at the Medical College of Ohio. "It has too many
effects."
So researchers are looking beyond nicotine to try to come up with
compounds that will act more specifically. Neuroscientist Edward Levin
and colleagues at Duke University are working with a nicotine-like
compound, AR-R 17779, that appears to improve learning and memory in
rats. Levin focuses on what are known as "alpha-7 nicotinic receptors,"
which are found in great concentrations in the hippocampus, part of the
brain important to memory and learning.
Receptors are cellular locks that wait for a chemical with a specific
shape to act like a key and trigger functions within the cell. In
nicotinic receptors, nicotine fits the locks meant for acetylcholine
(ACh), one of the body's natural receptor keys.
When Levin and his colleagues injected rats with the chemical, the rats
were able to run mazes more effectively. The researchers then took the
study a step further by giving the drug to rats whose memories had been
impaired by damaging pathways to the hippocampus. Those rats improved as
well -- a hopeful sign for Alzheimer's research because the connection
to the hippocampus is often damaged in victims of that disease.
Researchers at R.J. Reynolds have also been working with nicotine
mimics, and have found similarly encouraging results. Two compounds,
known as RJR-2557 and RJR-1734, also trigger the brain's ACh receptors.
R.J. Reynolds researcher Patrick Lippiello gave the drugs to
rats and found that the compounds boosted short-term and long-term
memory. The effects last about 18 hours in rats, and the drugs can be
taken orally.
The chemicals also seemed to protect rat brain cells from being
destroyed by some toxins, which could point the way to a therapy that
not only alleviates the symptoms of Alzheimer's but also prevents brain
cell degeneration.
Of course, a drug that triggers receptors can work only if there are
receptors to be triggered, and so the R.J. Reynolds researchers believe
their drug, if effective in humans, will best be used if the disease can
be caught in the early stages. "Early intervention in the disease would
be a must," Lippiello said.
Any human therapies based on these drugs would be years away, Lippiello
warned.
Seth Moskowitz, an R.J. Reynolds spokesman, said the company's venture
into the drug business should not be taken as an admission that it is in
the drug trade. "The work that we're doing in this area is totally
separate and apart from our cigarette business," Moskowitz said. "It
started about nine or 10 years ago with the realization that we have a
lot of expertise and knowledge about nicotine." R.J. Reynolds is now
planning to begin clinical trials on the drugs through a partner in the
pharmaceutical industry.
Aong with the new nicotine mimics, many researchers believe that
old-fashioned nicotine still has a role to play.
Paul R. Sanberg, professor and chair of neuroscience at the University
of South Florida, said about 80 percent of his patients in a study of
nicotine patches for Tourette's syndrome, a neurological disorder marked
by uncontrollable tics, have "shown improvement in both decreasing the
frequency and the intensity of the tics" with long-term effects. In a
seeming paradox, giving patients drugs that block the action of nicotine
also seems
to lessen their Tourette's symptoms. No one yet knows why, but it may be
because nicotine desensitizes receptors it works on -- in effect making
it its own blocker.
Other medical mysteries await researchers. The exceptionally high rates
of smoking among people afflicted with Attention Deficit Hyperactivity
Disorder (ADHD), depression and schizophrenia suggest that nicotine and
similar chemicals might provide some relief. Studies have already shown
an improvement in cognitive ability among schizophrenics and a greater
ability to focus among ADHD patients who wear a nicotine patch.
Abbott Laboratories is working with researchers at the National
Institutes of Health to study a nicotine-like drug from the skin of
Amazonian frogs used for poison darts that is, in smaller doses, a
highly effective painkiller.
And Esther Sabban at New York University Medical College is exploring
the role of nicotine in relieving the ill effects of stress on the body.
But what about addiction? Sanberg said he has given nicotine in patch
form to children as young as 8 who suffer from Tourette's. "There were
clearly people that didn't like the idea of giving their children
nicotine and the thought that maybe they could get addicted or start
smoking," he said. Nicotine in patch and gum form does not appear to
carry the risk of addiction that smoking does, Sanberg said: In
cigarettes, the first puff sends a potent jolt of the drug directly to
the brain in about eight seconds, while patches and gum work far more
slowly and consistently. "We haven't seen any addiction," Sanberg said.
Compared with the usual treatments for the disease, including potent
antipsychotic drugs with side effects that can be severe, parents
generally opt for the nicotine treatment, Sanberg said.
Scientists studying nicotine say that even if the drug can be addicting,
that side effect is something that society will tolerate if the benefits
outweigh the risks. Opiates, Levin noted, "can produce an awful
addiction -- but if you're in severe pain, it's a godsend."
Nicotine: The Benefits and the Detriments
POSITIVE EFFECTS
* Analgesic: Relieves pain without diminishing the sense of touch.
* Cognitive enhancement: Increases process involved in thinking and
knowing.
* Cerebrovasodilation: Dilates the blood vessels of the brain.
* Neuroprotection: Protects cells of nervous system from certain
degenerative diseases. Appears to protect some neurons from Alzheimer's
disease.
* Anxiolysis: Lowers anxiety levels.
* Antipsychotic: Helps maintain connection with reality. Untreated
psychotic people are more likely to smoke than are non-psychotics.
NEGATIVE EFFECTS
* Gastrointestinal distress: Digestive problems; stomach upset, bowel
cramping, constipation, etc.
* Hypothermia: Lowers body temperature to below-normal levels.
* Emesis: Vomiting.
* Hypertension: Blood vessels constrict to create high blood pressure in
some people, increasing potential for aneurysms.
* Seizures: Uncontrolled electrical activity in the brain, resulting in
tremors and other abnormal responses.
* Respiratory distress: Nodules, de generation and vasoconstriction in
the lungs. Increases the potential for development of small cell lung
carcinomas by several hundred percent.
SOURCE: Phyllis C. Pugh
© Copyright 1998 The Washington Post
--
Judith Richards, London, Ontario, Canada
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