Posted by AndrewB on January 2, 2001, at 1:31:43
In reply to Re: S.D.- some more thoughts » judy1, posted by SLS on January 1, 2001, at 21:26:25
Scott,
Thank you for the provocative info. on lamotrigine's dopaminergic effects.
Though it not clear to me how lamotrigine achieves its mood and antidepressive actions I thought I would add some possibly relevant factoids to the discussion.
Antidepressants (when effective) cause upregulation of the D2/(D3?) receptors in the shell of the nucleus accumbums (a site associated with mood and anxiety) and downregulation of the NMDA receptors.
The major neurotransmitter pathways to the shell of the nucleus accumbuns are dopaminergic, of course, and glutaminergic.
NMDA is one of the three glutaminergic receptors subtypes along with the AMPA and Kainate receptors.
Possibly NMDA antagonism is the route by which antidepressants upregulate the D2/D3 receptors.
NMDA antagonists can exhibit antidepressant effects.Abnormal glutaminergic transmission, especially involving the NMDA receptor, is associated with depression.
Abnormal glutaminergic transmission is associated with bipolar disorder.
Combined AMPA and Kainate receptors antagonists are potent anticonvulsants.
AMPA and NMDA receptor antagonists can act synergistically to provide robust anticonvulsant action at doses that do not produce behavioral side effects.
(It seems that glutamate receptor antagonists hold great promise for side effect free control of bipolar cycling.)
The partial NMDA antagonist Memantine (available from overseas) increases the effectiveness of Depakote for bipolar disorder without extra side effects.
(I wonder if Memantine may also increase the effectiveness of Lamotrigine. One study showed that Lamotrigine increased the mood elevating effects of ketamine, a total NMDA antagonist, and decreased its cognitive impairment.)
In sum, Lamotrigine’s effectiveness in controlling cycling may well involve actions on all the glutamate receptors, while its mood effects may be primarily dopaminergic mediated through the NMDA receptors.
poster:AndrewB
thread:50592
URL: http://www.dr-bob.org/babble/20001231/msgs/50722.html