Posted by mattdds on January 27, 2003, at 8:35:53
In reply to Questions about Benzo's/GABA, and AED's!!!, posted by titleistguy on January 26, 2003, at 23:37:14
Sean,
Also, to answer your question about mechanism of action of BZD's:
The benzos actually act indirectly on GABA, through the benzodiazepine receptor, or BZD receptor. The BZD receptor is part of a receptor complex surrounding a chloride channel. Basically, when benzos bind BZD receptors, it makes it easier for GABA to exert its action, which is opening chloride channels on neurons. Opening chloride channels on CNS neurons hyperpolarizes (stabilizes) their membranes, so they can't fire as easily. You can see why this would be helpful for anxiety: it calms hyperactive neurons that are sending messages for you to panic!
As for the BZD-1 / BZD-2 thing. BZD-1 and 2 are both associated with GABA-A, which is the GABA subtype associated with anxiety. BZD-1 receptors are thought to be involved in sleep and sedation, while BZD-2's involve anti-anxiety, and anti-convulsant effects. The GABA-B receptors aren't important in anxiety. Interestingly, however, baclofen, which is a centrally acting muscle relaxant, binds GABA-B. Also, GABA-B might be involved in blood pressure regulation.
You asked about different drugs that effect GABA/BZD receptors. Actually, alcohol, barbiturates, chloral hydrate (a favorite of my dental colleagues :), I prefer the benzos) also increase GABA activity, but in a much "dirtier" fashion, i.e. they affect a whole slew of other things in the process. These other agents do not work via the BZD receptor, but *directly* on the GABA receptor. Ambien (zolpidem tartrate) is a selective BZD-1 receptor agonist. Remember BZD-1 is involved in sleep, BZD-2 is anxiety and muscle relaxation. So this explains why Ambien is good for sleep, but not so much for anxiety or muscle relaxation. Interestingly, Klonopin and Xanax, both of which are thought to be less sedating and very specific for anxiety and panic, are both more selective for BZD-2 receptors.
One interesting animal study of benzodiazepines looked at macaque monkeys with damage to the septal area of the brain, making them extremely irritable and anxious. The experimenters used either barbiturates or benzodiazepines to tame these crazy monkeys. Both BZD's and barbs calmed them, but with the barbs, the amount required for anxiolysis also heavily sedated the monkeys; while the benzodiazepines caused no sedation, but got rid of all the irritability and anxiety. This suggests that benzos have selective antianxiety effects. They can calm without sedation, at the right doses (although your 2.5 mg of Klonopin was probably way too much to start with...into the sedation dosage range!!).
So benzos are quite remarkable drugs. Sure there are others that enhance GABA-ergic transmission (alcohol, barbiturates, chloral hydrate, valproate, etc.) but *none* is as specific for anxiety (not to mention as safe) as the good ol' benzos.
I hope this helps a little.
Matt
poster:mattdds
thread:137721
URL: http://www.dr-bob.org/babble/20030125/msgs/137756.html