John L Neumeyer

Novel Phenyltropanes: Affinity to Monoamine Transporters in Rat Forebrain

The active, natural (-)-isomer of cocaine (compound 1; Figure 1) preferentially binds to dopamine transporter (DAT) proteins in the cell membranes of DA neurons, with lesser interactions at transporters for norepinephrine (NET) and serotonin (5-hydroxytryptamine, 5-HTT) (Harris and Baldessarini, 1973; Reith et al, 1980; Kennedy and Hanbauer, 1983; Calligaro and Elderfrawi, 1987, 1988; Madras et al., 1989). The DAT is essential to the major physiological process for inactivating DA released extracellularly at synapses by neuronal reuptake, Its inhibition by cocaine or other psychostimulant drugs enhances dopaminergic neurotransmission in the forebrain (Reith et al., 1986; Ritz et al., 1987; Bergman et al., 1989). Saturable binding sites for (-)-cocaine at the DAT associated specifically with DA-containing nerve terminals have been identified in caudate-putamen (neostriatum) tissue in the forebrain of rodents (Calligaro and Elderfrawi, 1988), nonhuman primates (Madras et al., 1989), and man (Schoemaker et al., 1985).