Effect of metadoxine on striatal dopamine levels in C57 black mice.
In the present study, we examined the effect of metadoxine on striatal levels of dopamine, 5-hydroxytryptamine (5-HT) and their metabolites in male C57 Black mice. Striatal content was assayed after systemic administration of metadoxine ranging from 1 micrograms kg-1 to 500 mg kg-1. Striatal dopamine increased 1 h after treatment with metadoxine (150 mg kg-1), but the most notable effect was obtained 24 h after the drug administration. At this time a plateau was reached; the two major metabolites of dopamine showed the same trend. Seven days after metadoxine administration, striatal dopamine approached the control values. Over the same time intervals, striatal 5-HT increased to a lesser extent and 5-hydroxy-indoleacetic acid did not differ significantly from controls. Striatal dopamine increased significantly at a dose of 250 micrograms kg-1 up to a dose of 1 mg kg-1 metadoxine; no further increment was observed between 1 and 500 mg kg-1 metadoxine. Administration of each component at doses equimolar to 1 mg metadoxine showed that pyridoxine produced only a mild increase in striatal dopamine compared with controls. We suggest that the metadoxine-induced striatal dopamine increase is obtained by increasing synthesis of dopamine.
Fornai
F
F
Institute of Pharmacology, School of Medicine University of Pisa, Italy.
Grazia Alessandrì
M
M
Bonuccelli
U
U
Scalori
V
V
Corsini
G U
GU
D000818:Animals; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011736:Pyridoxine / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
D004338:Drug Combinations; D012701:Serotonin; C037845:metadoxine; D011736:Pyridoxine; D011761:Pyrrolidonecarboxylic Acid; D004298:Dopamine