Neurochemical effects of the monoamine oxidase inhibitor phenelzine on brain GABA and alanine: A comparison with vigabatrin.
PURPOSE: To compare phenelzine (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T). METHODS: Male rats were administered PLZ (10 mg/kg) or VIG (1,000 mg/kg) i.p., and the rats were euthanized 4 hours later and the brains removed for analysis of levels of GABA and ALA (by electron capture gas chromatography after derivatization) and activities of MAO, GABA-T and ALA-T (radiochemical assays). RESULTS: Both PLZ and VIG inhibited GABA-T and elevated GABA levels. Only PLZ inhibited MAO and ALA-T and elevated ALA levels. The effects of PLZ on both amino acids and their transaminases were blocked by pre-treatment with the MAO inhibitor tranylcypromine. This pretreament had no effect on the inhibition of GABA-T or the elevation of brain GABA levels produced by VIG. CONCLUSIONS: At the doses studied, PLZ was as effective as VIG at elevating brain GABA levels, but, unlike VIG, also inhibited MAO and ALA-T (and increased brain ALA levels). Pretreatment of rats with the MAO inhibitor tranylcypromine prevented the increase in brain GABA and ALA levels with PLZ, but did not block the effect of VIG on GABA. These observations with tranylcypromine and PLZ support the hypothesis that an active metabolite of PLZ produced by the actions of MAO on this drug plays a major role in its GABA- and ALA-elevating actions.
T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T20 T21 T22 T23 T24 T25 T26 T27 T28 T29 T30 T31 T32 T33 T34 T35 T36 T37 T38 T39 T40 T41 T42 T43 T44 T45 T46 T47 T48 T49 T50 T51 T52 T53 T54 T55 T56 T57 T58 T59 T60 T61 T62 T63 T64 T65 T66 T67 T68 T69 T70 T71 T72 T73 T74 T75 T76 T77 T78 T79 T80 T81
CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N GENE-Y GENE-N GENE-N GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-N GENE-Y GENE-N GENE-N GENE-N GENE-Y GENE-N GENE-Y GENE-N GENE-N GENE-N GENE-N
tranylcypromine monoamine GABA GABA VIG PLZ VIG GABA VIG ALA ALA tranylcypromine GABA ALA PLZ VIG GABA tranylcypromine PLZ PLZ GABA ALA amino acids aminobutyric acid GABA phenelzine alanine ALA vigabatrin VIG GABA GABA PLZ GABA GABA ALA GABA ALA ALA PLZ VIG GABA ALA GABA ALA PLZ VIG GABA GABA PLZ ALA ALA PLZ amino acids vigabatrin monoamine phenelzine GABA alanine MAO monoamine oxidase GABA-T MAO MAO ALA-T MAO MAO GABA transaminase GABA-T MAO GABA-T ALA transaminase ALA-T MAO GABA-T ALA-T GABA-T MAO ALA-T transaminases monoamine oxidase