Posted by Shawn. T. on April 15, 2003, at 20:27:15
In reply to Re: Please help with my list of promising future drugs, posted by jaby on April 14, 2003, at 11:52:41
Regarding the NMDA antagonists, I don't believe that the likelihood of FDA approval of these drugs for psychiatric disorders is especially high. I'm also looking for drugs that get right to the source of the problem.
The question on Lamictal is challenging... here is my description of Lamictal's (lamotrigine) mechanism of action:
Lamotrigine blocks use- dependent voltage- sensitive sodium channels. The drug preferentially binds to the channel pore in inactivated but not resting sodium channels; its inhibition of sodium channels is therefore increased by neuronal depolarization. Lamotrigine also inhibits N-type and P/Q-type voltage- activated calcium channels.
-I find it difficult to argue that its mechanism of action that leads to efficacy in say bipolar disorder is solely sodium channel blockade. I'm not sure what role its actions at voltage- gated calcium channels play, but I'll speculate and say that they're probably less important. Likewise, both types of effect are probably important for its efficacy as an anticonvulsant.
With regards to the activating component of Lamictal, a reduction in glutamate release by the drug is likely responsible. (See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10496235&dopt=Abstract ). The drug reduces glutamate release via its actions on sodium channels and perhaps N-type calcium channels (I'm not sure about P/Q-type channels). An alternative explanation for Lamictal's activating effect is that it negatively modulates the effects of GABA (see http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11955522&dopt=Abstract ); I can't offer any proof for this idea, so it's pure speculation.
Riluzole seems to be a neuroprotective drug used to treat amyotrophic lateral sclerosis/ motor neuron disease. I believe that it acts similarly to Lamictal (See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12645037&dopt=Abstract ). I believe that riluzole may be more potent at sodium channels than Lamictal. If you need any references on any of this, I'd be glad to give them to you.
Shawn
poster:Shawn. T.
thread:219077
URL: http://www.dr-bob.org/babble/20030411/msgs/219664.html