THIQ question

Matt Jones jonesmat at ohsu.edu
Tue Aug 3 20:00:44 EST 1999


In article <7o5iig$44f at dfw-ixnews15.ix.netcom.com> Anonymous,
user1804 at abcflash.net writes:
>As far as I understand, THIQ (tetrahydro isoquinoline) is an opiate-like
>molecule
>produced in the brain of heroin users. It is also formed in some alcoholics
>over time. Alcohol normally breaks down into acetaldehyde, then into H2O and
>CO2. But in some
>

>>Are there any known substances which are
>>capable of attaching themselves to THIQ molecules in the brain and removing
>>them from the receptor site they are attached to?  


Apparently THIQ binds to several receptors or enzymes, including
phenylethanolamine-N-transferase (catalyzes the production of the
neurotransmitter epinephrine), the alpha-2 adrenergic receptor,
muscarinic and opioid receptors.

The problem with the idea of designing a compound to remove THIQ from its
receptors is that that's not really the way molecules interact. The
potency of a drug is the ratio of its unbinding rate to its binding rate.
Both binding and unbinding are random processes that can be characterized
by average rates. The binding rate depends on this intrinsic rate
constant and also on the concentration of the drug. But the unbinding
rate depends only on the intrinsic stability of the complex formed by the
drug and the receptor site together.  Once these things are bound to each
other, the only practical way to separate them is to sit and wait for
them to fall apart (by random motion), at which time you can try to
remove the disagreeable substance from the environment of the receptor
(scavengers, metabolising enzymes, uptake transporters, or just simple
clearance by diffusion). Alternatively you can try to prevent its
re-binding by adding another molecule that binds to the same site
(competition).

I read somewhere that naloxone or naltrexone (opioid receptor
antagonists) were being tried to help in alcoholism, the idea being that
they would compete with THIQ. This hasn't been remarkably successful.
Ethanol itself has so many effects on different neurotransmitter systems
and enzymes that it seems unlikely that there will be a simple unitary
solution.

Matt Jones



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