The effect of etidocaine on spontaneous and evoked release of norepinephrine from rat brain synaptosomes.
Local anesthetics have been shown to have an effect on neurotransmission. In this study we examined the effect of a local anesthetic, etidocaine, on the uptake, efflux, and release of norepinephrine (NE) from central nerve terminals. The studies were performed on synaptosomes and vesicles prepared from rat brains. Etidocaine 10(-4) M inhibited synaptosomal accumulation of [3H]NE and did not significantly effect vesicular accumulation of this neurotransmitter. This concentration of etidocaine also augmented efflux of norepinephrine from synaptosomal preparations. This augmented efflux was primarily due to an increase in the deaminated metabolite 3,4-dihydroxyphenylglycol (DOPEG). The presence of etidocaine did not significantly alter the release of NE from synaptosomes superfused with high potassium (40 mM), a calcium-dependent exocytotic release process. These results indicate that in the central nervous system, as previously demonstrated in the peripheral nervous system, high concentrations of etidocaine alter vesicular storage of NE, resulting in more NE leaking into the cytoplasm where it is metabolized to an inactive metabolite.
D000083:Acetanilides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003864:Depression, Chemical; D005041:Etidocaine / Q000494:pharmacology*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000096:biosynthesis; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D000083:Acetanilides; D000779:Anesthetics, Local; D008734:Methoxyhydroxyphenylglycol; D012110:Reserpine; D005041:Etidocaine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine