Posted by desolationrower on December 16, 2008, at 22:45:06
In reply to MAOI plus Sam-E, posted by uncouth on December 13, 2008, at 17:40:46
I came across this. I hadn't been aware of these effects. It might indicate SAMe might be good to add.
7. S-Adenosyl-L-Methionine-Saving Effect of COMT Inhibitors. It is well known that the levodopa therapy in PD patients depletes their body levels of AdoMet levels, and this depletion also occurs in the brain (Benson et al., 1993). This can be explained by enhanced O-methylation of the large doses of L-dopa present, which consumes the methyl groups of AdoMet. Long-term levodopa treatment leads to compensatory enhancement of the synthesis of AdoMet by increasing the activity of methionine adenosyl transferase (Benson et al., 1993). In turn, when high doses of exogenous AdoMet were administered, they depleted nigrostriatal and forebrain tyrosine hydroxylase and brain dopamine (Charlton, 1997). When the COMT-induced O-methylation was effectively inhibited by first-generation COMT inhibitors (like tropolone but not pyrogallol; Waldmeier and Feldtrauer, 1987) and second-generation compounds (like tolcapone; Da Prada et al., 1994; Miller et al., 1997; Yassin et al., 1998), AdoMet levels in the brain were increased. Homocysteine levels were restored by tolcapone (Da Prada et al., 1994; Miller et al., 1997). Tolcapone enhanced the activity of methionine adenosyl transferase (Yassin et al., 1998). Even CGP 28014, an atypical inhibitor of O-methylation that does not inhibit the COMT enzyme itself, elevated AdoMet levels in the brain (Waldmeier et al., 1990a). Interestingly, MAO inhibition appeared to have just the opposite effect as that observed after COMT inhibition (Yassin et al., 1998).
Enhanced AdoMet levels in the brain during tolcapone therapy may explain the antidepressive (Moreau et al., 1994; Männistö et al., 1995) and cognition-improving (Khromova et al., 1995, 1997) effects of COMT inhibitors. Some studies have shown that the quality of life is increased in PD patients receiving COMT inhibitor therapy (Welsh et al., 1995; Baas et al., 1997; Waters et al., 1997). One report has also described improved cognition during tolcapone therapy (Gasparini et al., 1997). In fact, these findings fit well to the animal data demonstrating both antidepressive and cognition-improving properties of COMT inhibitors (Moreau et al., 1994; Männistö et al., 1995; Khromova et al., 1997; Liljequist et al., 1997).
It may be that MAOIs make SAMe be used, or are powerful antidepressants DESPITE reducing SAMe. Also,
Oral creatine supplementation attenuates L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rats
L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson patients after a prolonged treatment with levodopa (L-DOPA). Since previous transcriptome and proteomic studies performed in the rat model of LID suggested important changes in striatal energy-related components, we hypothesize that oral creatine supplementation could prevent or attenuate the occurrence of LID. In this study, 6-hydroxydopamine-lesioned rats received a 2% creatine-supplemented diet for 1 month prior to L-DOPA therapy. During the 21 days of L-DOPA treatment, significant reductions in abnormal involuntary movements (AIMs) have been observed in the creatine-supplemented group, without any worsening of parkinsonism. In situ hybridization histochemistry and immunohistochemistry analysis of the striatum also showed a reduction in the levels of prodynorphin mRNA and FosB/ΔFosB-immunopositive cells in creatine-supplemented diet group, an effect that was dependant on the development of AIMs. Further investigation of the bioenergetics status of the denervated striatum revealed significant changes in the levels of creatine both after L-DOPA alone and with the supplemented diet. In conclusion, we demonstrated that combining L-DOPA therapy with a diet enriched in creatine could attenuate LID, which may represent a new way to control the motor complications associated with L-DOPA therapy.
I wonder if SAMe, which something like 40% goes to production of creatine i think, would also help. We have seen small scale study of that creatine is antidepressent effective. At minimum i think creatine should be along with MAOI taken EXCEPT by bipolars.