Mode of benzodiazepine action

Dr. Alan Wheatley rawheatley at canadalane.demon.co.uk
Tue Dec 15 14:54:41 EST 1998


This month's "Chemistry in Britain", the magazine of the Royal Society of
Chemistry, carries an article by one of their in-house writers on drug
addiction entitled "Drugs against drugs".  While the article is
interesting, it seems to be at conflict with my previous understanding of
the mode of action of benzodiazepines.  The article suggests that
addiction results from an increase in dopamine activity:  "It is thought
that all habit-forming drugs affect the dopamine (DA) system in the brain
either directly as DA agonists, or by enhancing DA release, or by acting
on other neurons responding to different neurotransmitters, which synapse
upon this DA system to activate it."  The benzodiazepines are explicitly
included in this explanation:  "Depressant drugs such as alcohol,
benzodiazepines, barbiturates and opiates virtually all act on the
gamma-aminobutyric acid (GABA) inhibitory neurotransmitter system.  These
substances indirectly affect the DA system by lowering the threshold of
its activation."  There is an accompanying diagram, showing a GABAergic
neuron synapsing directly onto a dopaminergic neuron.  When I last had
reason to consider this matter, several years ago, the prevailing view was
that the principal action of benzodiazepines was the production of
inhibitory GABA-like effects that led to a reduced turnover of monoamines
in the brain.  Does that view still hold?  If so, are the quotes from the
article simply wrong, or do the benzodiazepines come within the category
"acting on other neurons responding to different neurotransmitters, which
synapse upon this DA system to activate it"?  I should welcome any light
that can be thrown on this apparent discrepancy, please.

Dr. Alan Wheatley at www.canadalane.demon.co.uk



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