Exploring the effect of N-substitution in nor-lobelane on the interaction with VMAT2: discovery of a potential clinical candidate for treatment of methamphetamine abuse.
A series of N-substituted lobelane analogues was synthesized and evaluated for their [(3)H]dihydrotetrabenazine binding affinity at the vesicular monoamine transporter and for their inhibition of vesicular [(3)H]dopamine uptake. Compound 19a, which contains an N-1,2(R)-dihydroxypropyl group, had been identified as a potential clinical candidate for the treatment of methamphetamine abuse.
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CHEMICAL GENE-N GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
nor-lobelane vesicular monoamine transporter VMAT2 N monoamine [(3)H]dopamine N-1,2(R)-dihydroxypropyl lobelane methamphetamine [(3)H]dihydrotetrabenazine methamphetamine N