Synthesis and characterization of selective dopamine D2 receptor antagonists

摘要: Abstract A series of indole compounds have been prepared and evaluated for affinity at D2-like dopamine receptors using stably transfected HEK cells expressing human D2, D3, or D4 receptors. These share structural elements with the classical receptor antagonists, haloperidol, N-methylspiperone, benperidol. The that N-methylspiperone benperidol bind non-selectively to D2 D3 subtypes. However, several structurally similar haloperidol were found (a) subtype nanomolar affinity, (b) be 10- 100-fold selective compared receptor, (c) low subtype. Binding sigma (σ) subtypes, σ1 σ2, also examined it was position methoxy group on pivotal in both versus selectivity Adenylyl cyclase studies indicate our greatest are neutral antagonists With (hD2-HEK), these no intrinsic activity attenuated quinpirole inhibition adenylyl cyclase. identified represent unique pharmacological tools potential use relative contribution subtypes physiological behavioral situations where dopaminergic involvement is indicated.