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"The nonselective monoamine transporter inhibitorRTI-126 and the DAT-selective inhibitors RTI-150 and RTI-336 both had a faster rate of onset (30 min) and a short duration of action (4h). In contrast, the nonselective monoamine transporter inhibitor RTI-112 had a slower rate of onset (30–60 min) and a longer duration of action (10h). The DAT-selective inhibitors RTI-171 and RTI-177 also had slower rates of onset (30–120 min), but RTI-171 had a short duration of action (2.5 h) while RTI-177 had a very long duration of action (20 h)."
The efficacy of cocaine analogs to elicit self-administration is related to the rate at which they are administered.[clarification needed] Slower onset analogs are less likely to function as behavioral stimulants than analogs eliciting a faster rate of onset. Nonselective analogs are less likely to function as "reinforcers" than reuptake inhibitors that have DAT specificity.
RTI-112 has equipotent in vitro affinity at the SERT, NET and DAT, respectively. RTI-112 was not reliably self-administered, in contrast to the DAT selective reuptake inhibitors that were used in this study. In vivo at the ED50, RTI-112 had no DAT occupancy at all. At the ED50, almost all of the RTI-112 occupied the SERT at this dose. A significantly higher dose was required to get >70% DAT occupancy in the case of RTI-112; however, RTI-112 was still able to suppress cocaine administration at the ED50, suggesting a serotonergic mechanism was responsible for this.
^ Ginsburg, B.C., Kimmel, H.L., Carroll, F.I., Goodman, M.M., Howell, L.L. Interaction of cocaine and dopamine transporter inhibitors on behavior and neurochemistry in monkeys. Pharmacology Biochemistry and Behavior, 80: 481-491, 2005.
^ abcdefg Lindsey, K.P., Wilcox, K.M., Votaw, J.R., Goodman, M.M., Plisson, C., Carroll, F.I., Rice, K.C., Howell, L.L. (2004) "Effects of dopamine transporter inhibitors on cocaine self-administration in rhesus monkeys: relationship to transporter occupancy determined by positron emission tomography neuroimaging." Journal of Pharmacology and Experimental Therapeutics, 309: 959-969
^ Howell, L.L. and Wilcox, K.M. "The dopamine transporter and cocaine medication development: Drug self-administration in nonhuman primates." Journal of Pharmacology and Experimental Therapeutics, 298: 1-6, 2001.
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