Investigation of the presynaptic effects of quinine and quinidine on the release and uptake of monoamines in rat brain tissue.
Quinine and quinidine are reported to potentiate the behavioural effects of serotonergic agents and monoamine uptake inhibitors. We have therefore investigated the presynaptic actions of quinine and quinidine on monoamine uptake and release in rat brain tissue in vitro. Quinidine evoked the release of [3H]5-HT, [3H]noradrenaline and [3H]dopamine from pre-loaded rat brain slices in a concentration dependent manner with EC50 values of 175, 486 and 150 microM, respectively. Quinine induced [3H]monoamine release with similar potencies. Both quinine and quinidine also inhibited the active uptake of [3H]5-HT, [3H]noradrenaline and [3H]dopamine into rat brain synaptosomes with IC50 values in the range 0.13-12.4 microM. The potency of each drug to inhibit [3H]5-HT uptake was significantly higher than that for [3H]noradrenaline or [3H]dopamine. The relative potency of quinidine compared to quinine was more marked in the case of [3H]5-HT (58-fold) than for [3H]noradrenaline (3-fold) or [3H]dopamine (4-fold). The inhibition of [3H]5-HT uptake by quinine and quinidine was competitive in nature and corresponded with the potencies of these drugs to inhibit [3H]paroxetine binding. No correlation was observed between the potencies of quinine and quinidine to induce the release of [3H]monoamines and to inhibit their uptake, suggesting that these effects are mediated by two distinct mechanisms. We conclude that the presynaptic actions of quinine and quinidine on monoamine uptake and release may be implicated in their potentiation of the effects of serotonergic agents and uptake blockers.
Oxford University SmithKline Beecham Centre for Applied Neuropsychobiology, University Department of Clinical Pharmacology, Radcliffe Infirmary, UK.
E M
EM
Clement
D G
DG
Grahame-Smith
J M
JM
Elliott
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D017374:Paroxetine / Q000493:pharmacokinetics; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011802:Quinidine / Q000494:pharmacology*; D011803:Quinine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*
D015306:Biogenic Monoamines; D009419:Nerve Tissue Proteins; D012701:Serotonin; D017374:Paroxetine; D011803:Quinine; D011802:Quinidine; D004298:Dopamine; D009638:Norepinephrine