Limpet_Chicken
Bluelighter
- Joined
- Oct 13, 2005
- Messages
- 6,323
Vigabatrin is an anticonvulsant, acting as a suicide inhibitor of GABA-transaminase, thus leading to increased stimulation of GABAa/GABAb/GABAc receptors.
various theories abound as to the modality of the optic toxicity, enzyme inhibition of various substrates, ornithine decarboxylase amongst others., lack of taurine, etc.
What concerns me is, the potential for excitotoxicity mediated via GABAcRs (I don't take vigabatrin mind you, couldn't pay me enough to touch the stuff outside of a petri dish, either via direct stimulation of GABAcRs causing calcium influx directly, or increased stimulation of GABAcRs via the indirect mechanism of increased GABA concentrations around the macula/retina area resulting in the same thing.
Primary substances in question for this here would be rosmarinic acid, a major compound in lemon balm (Melissa officianalis), apparently its a pretty strong GABA-T inhibitor, anyone know if its reversible, or a suicide inhibitor like vigabatrin?
And muscimol, which aside from being a potent (and until recently I was under the impression, highly selective) GABAa agonist, selective for the orthosteric binding site. Turns out its also a GABAc agonist also. What I'm not sure of is relative affinity and efficacy (vs GABA) at the optic area expressed GABAcR vs GABAaRs.
One would have to drink a bloody metric ton of fly agaric tea, I'm sure, to screw one's eyes over, but, with vigabatrin, it appears that the tendency to cause retinopathies is patient specific rather than following any linear dose-response curve or correlating with quantities taken over a lifetime
And before anyone says the same thing about balm...Its pretty benign as a herb as far as everything I have ever known of can cite, but I have to admit, I can slug the stuff down by the liter like a terminal coffee addict downs espresso. In fact, I have ended up outpacing my plants growth at times, which takes quite some doing, stuff spreads like plague in rat-flea soup.
various theories abound as to the modality of the optic toxicity, enzyme inhibition of various substrates, ornithine decarboxylase amongst others., lack of taurine, etc.
What concerns me is, the potential for excitotoxicity mediated via GABAcRs (I don't take vigabatrin mind you, couldn't pay me enough to touch the stuff outside of a petri dish, either via direct stimulation of GABAcRs causing calcium influx directly, or increased stimulation of GABAcRs via the indirect mechanism of increased GABA concentrations around the macula/retina area resulting in the same thing.
Primary substances in question for this here would be rosmarinic acid, a major compound in lemon balm (Melissa officianalis), apparently its a pretty strong GABA-T inhibitor, anyone know if its reversible, or a suicide inhibitor like vigabatrin?
And muscimol, which aside from being a potent (and until recently I was under the impression, highly selective) GABAa agonist, selective for the orthosteric binding site. Turns out its also a GABAc agonist also. What I'm not sure of is relative affinity and efficacy (vs GABA) at the optic area expressed GABAcR vs GABAaRs.
One would have to drink a bloody metric ton of fly agaric tea, I'm sure, to screw one's eyes over, but, with vigabatrin, it appears that the tendency to cause retinopathies is patient specific rather than following any linear dose-response curve or correlating with quantities taken over a lifetime
And before anyone says the same thing about balm...Its pretty benign as a herb as far as everything I have ever known of can cite, but I have to admit, I can slug the stuff down by the liter like a terminal coffee addict downs espresso. In fact, I have ended up outpacing my plants growth at times, which takes quite some doing, stuff spreads like plague in rat-flea soup.