Posted by Cam W. on October 22, 2001, at 23:12:37
In reply to Re: Proposed Mechanisms of Action of Lamotrigine » Cam W., posted by JohnX on October 20, 2001, at 11:48:09
John - The difference between pre- and post-synaptic receptor agonists and antagonists (like NMDA antagonists) and sodium ion (Na+) (like lamotrigine) and calcium ion (Ca2+) (like nifedipine) blockers is that the former acts between 2 neurons and the latter is on an axon of one neuron.
When talking about NMDA (D2, 5-HT2, alpha-1, etc) antagonists we usually mean that we are either blocking the signal on the post-synaptic membrane. These drugs block post-synaptic receptors and do not allow the natural neurotransmitter to stimulate the receptor and thus the signal carried by the neurotransmitter is blocked (for NMDA receptors the neurotransmitter is glutamate; for D2 it is dopamine; for 5-HT2 it is serotonin).
Agonists on the other hand act like the neurotransmitter and cause a signal to go through (causing the neuron to fire) without the presence of a neurotransmitter, when the receptor for the agonist is on the post-synaptic membrane.
When on the pre-synaptic membrane (eg. 5-HT1A on the somatodentritic surface - neuron cell body; or 5-HT1B on the axon terminal) agonist are usually stimulating autoreceptors, which act as a negative feedback mechanism. When stimulated (by agonists or neurotransmitters) autoreceptors shut off the flow of neurotransmitter from the pre-synaptic nerve terminal, slowing the electrical impulse from on neuron to another. When blocked by an antagonist the flow of transmitter is increased from the pre-synaptic terminal, increasing the eletrical flow from on neuron to another.
Then there are different agonists and antagonists. Noncompetitive antagonists block the receptor outright and are usually irreversible. Competitive antagonists compete with the neurotransmitter and can be displaced if the neurotransmitter level is high enough.
This is a very basic outline of agonists and antagonists, and I hope that you are able to wrap your brain around some of the logic. It actually took me a few years to figure it all out (and I still occasionally get thrown when combinations are working at the same time).
I hope that this is what you were looking for. - Cam
poster:Cam W.
thread:81710
URL: http://www.dr-bob.org/babble/20011015/msgs/82023.html