Posted by phidippus on January 18, 2014, at 2:35:43
In reply to Willyee ...NMDA ANTGONISTS., posted by brk23 on January 12, 2014, at 17:03:51
I take Rilutek. It has helped with both my OCD and my depression.
The mechanism of action of riluzole in the nervous system is complex. A considerable number of actions have been demonstrated in vitro, but some of these may have little relevance in vivo, where much lower concentrations of riluzole are achieved. Pittenger and colleagues have recently reviewed the subject very capably (Pittenger et al. 2008b).
Riluzole inhibits the release of glutamate at the presynaptic nerve cell terminus, most likely by blockade of voltage-gated sodium channels, and this effect may be achieved at low riluzole concentrations (demonstrated most recently by Urbani and Belluzzi 2000). It also likely reduces glutamate neurotransmitter vesicle fusion with the presynaptic cell membrane, either directly by opening voltage-gated calcium channels (Wang et al. 2004) or indirectly by altering G-proteinmediated signaling (Huang et al. 1997). Riluzole's effects on potassium channels have also been measured, but possibly not at clinically meaningful riluzole concentrations (Ahn et al. 2005; Mathie and Veale 2007).
Downstream effects of riluzole have been noted as well, but clinical significance remains unclear. These effects are stimulation of growth factor synthesis, including brain-derived neurotrophic factor (Fumagalli et al. 2006), and promotion of neuritogenesis, neurite branching, and neurite outgrowth (Shortland et al. 2006).
Riluzole has not been found to interact with any glutamate receptors at clinically meaningful concentrations (Habibi-Asl et al. 2009). However, enhancement of the hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor (GluR1, GluR2) subunit expression (Du et al. 2006) has been noted. And at high concentrations, there has been measured antagonism of AMPA and N-methyl-d-aspartate (NMDA) receptors (Pittenger et al. 2008b). Riluzole increases glial glutamate reuptake, possibly at the low levels found only extrasynaptically (Frizzo et al. 2004; Fumagalli et al. 2008).
In a recent study, riluzole (4 mg/kg, a reasonable dose when used in humans) attenuated the behavioral effects of chronic unpredictable stress, a rodent model of depression (Banasr et al. 2010). In the same study, the investigators demonstrated that metabolic and mRNA expression effects of stress were also attenuated by riluzole. These results are consistent with the evidence for the riluzole-enhanced reuptake of glutamate by glial cells. In addition, riluzole (10 μM) has been shown to exhibit a neuroprotective effect on rat glial cells to which a toxic level of glutamate (100 μM) was added in culture (Dagci et al. 2007).
There have been reports of riluzole effects on other neurotransmitters, but there has been little replication of these findings so far.
Eric
poster:phidippus
thread:1058422
URL: http://www.dr-bob.org/babble/20140104/msgs/1058868.html