Molecules could offer addictionfree morphine

LONDON, April 2 (Reuter) U.S. researchers said on Wednesday they had
identified two brain chemicals that strongly affect pain processes in the
brain and said they could be the key to how drugs like morphine and heroin
work.

Another expert said the two peptides could possibly even be used as
addictionfree painkillers.

James Zadina and colleagues of the Veterans Affairs Medical Centre and
Tulane University in New Orleans named the peptides endomorphin1 and
endomorphin2 and said they acted by themselves to ease pain in mice.

Writing in the science journal Nature, they said opiates such as morphine
were known to act on brain cell receptors a kind of keyhole known as mu
receptors. But no one had found the key, or ligand, that hooks the opiates to
the mu receptor.

Zadina's team painstakingly generated a series of peptides, which are
simple compounds composed of two or more amino acids. Each peptide in the
series had five amino acids in it and they substituted a different amino acid
one by one until they found one that would attach to the mu receptor.

They tried injecting it into the brains or spinal cords of mice and found
it worked just as well as morphine to kill pain.

They then looked for a similar peptide occurring naturally in cow's
brains and found two. They were found in areas of the brain such as the
thalamus that are known to contain receptors for opiate drugs.

They named the peptides endomorphin1 and endomorphin2. The names are
shortened versions of the descriptive phrase ``endogenous morphinelike''
substances.

David Julius, a molecular pharmacologist at the University of California,
San Francisco, raised the possibility that the molecules could be used as
painkillers themselves.

``Could the endomorphins provide relief from pain without eliciting the
negative symptoms that are associated with morphine, such as respiratory
depression, nausea, tolerance and addiction?'' Julius asked in an
accompanying commentary.

If nothing else, the discovery should spark a search for other, similar
peptides, he added.