Effect of methylene blue and related redox dyes on monoamine oxidase activity; rat pineal content of N-acetylserotonin, melatonin, and related indoles; and righting reflex in melatonin-primed frogs.
The ability of methylene blue (MB) to inhibit the nitric oxide-induced stimulation of N-methyl-D-aspartate receptors has been suggested as a possible mechanism of MB's clinical antidepressant action. This study evaluated the alternative/additional mechanisms of the antidepressant effect of MB on biochemical and behavior levels. Selective inhibition of monoamine oxidase type A (MAO-A) is widely accepted as a major mechanism of the clinical antidepressant effect. MB and the related redox dyes toluidine blue O (TBO), thionine (TN), brilliant cresyl blue (BCB), and toluylene blue (TB) were reversible competitive inhibitors of both MAO-A and MAO-B and were highly selective toward MAO-A. TBO was the most potent inhibitor, followed by TN, BCB, MB, and TB. The dyes studied increased rat pineal N-acetylserotonin (NAS) and melatonin content, in accordance with our previous observations of the stimulating effect of selective inhibition of MAO-A on pineal melatonin biosynthesis. The redox dyes exerted antidepressant-like activity in frogs; that is, they suppressed the righting reflex in melatonin-primed frogs. This study's results indicate that selective inhibition of MAO-A might mediate the clinical antidepressant effect of MB through NAS stimulation and melatonin biosynthesis.
Oxenkrug
G F
GF
Department of Psychiatry, Tufts University, 750 Washington St., Ste. 1007, Boston, MA 02111, USA. goxenkrug@tufts-nemc.org
Sablin
S O
SO
Requintina
P J
PJ
D000818:Animals; D001001:Anura; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008550:Melatonin / Q000378:metabolism*; D008751:Methylene Blue / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D010084:Oxidation-Reduction; D010870:Pineal Gland / Q000187:drug effects*; D051381:Rats; D012018:Reflex / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000378:metabolism
D004791:Enzyme Inhibitors; D012701:Serotonin; D008995:Monoamine Oxidase; D008550:Melatonin; C006389:N-acetylserotonin; D008751:Methylene Blue