Characterization of binding of [3H]GBR 12935 (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine) to membranes and to solubilized membrane extracts from terminal field regions of mesolimbic, mesocortical and nigrostriatal dopamine pathways

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amfonelic acid; cocaine; dopamine uptake; GBR 12935


The binding characteristics of [3H]GBR 12935 (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl-propyl)piperazine), a selective dopmaine uptake inhibitor, were examined in intact membrane preparations and solubilized extracts of terminal field regions of dopamine pathways in the brain of the rats. There were many similarities in the properties of binding sites for [3H]GBR 12935 in the striatum, nucleus accumbens and olfactory tubercle. The binding of [3H]GBR 12935 was saturable and the affinity constants were not significantly different between regions of the brain. The binding of [3h]GBR 12935 was inhibited by amfonelic acid, GBR 12909, mazindol, methylphenidate and cocaine, with comparable affinities in each region of the brain and with the same order of potency in both preparations. Furthermore, the rank order of potencies for inhibiting the binding of [3H]GBR 12935 was the same as for inhibiting the uptake of [3H]dopamine in these regions of the brain. There did appear to be some degree of heterogeneity of binding sites for [3H]GBR 12935 in each of these regions of the brain, as both amfonelic acid and mazindol were best fitted by two-site models. Whether this apparent heterogeneity was due to the existence of two distinct binding sites or to two components of a single site is unclear. It did not, however, appear to be due to binding to uptake sites for norepinephrine or serotonin, as neither nisoxetine nor fluoxetine, selective inhibitors of the uptake of norepinephrine and serotonin, respectively, inhibited the binding of [3H]GBR 12935, at concentrations which inhibit the uptake of norepinephrine or serotonin. © 1990.

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