The original definition of the D1 and D2 subtypes based on biochemical and pharmacological criteria noted the ability of certain drugs such as sulpiride and metoclopramide to act as antagonists of the D2 actions of dopamine but not the D1 actions. Subsequent work lead to the synthesis of selective antagonists SCH 23390 and raclopride for the D1 and D2 subtypes, respectively. Following the identification of the different dopamine receptor subtypes using molecular biological techniques, there have been active programmes to synthesize compounds more selective for D2-like receptor subtypes. Thus, a number of improvements on the prototypical agent raclopride's spectrum of higher affinity for D2 and D3 receptors than D4 receptors have been made. In particular, L741626, SB-277011-A, and L745870 are D2 selective (~40 fold), D3 selective (~100 fold), and D4 selective (~2000 fold) antagonists, respectively (Bowery et al. 1996; Stemp et al. 2000; Patel et al. 1997). The aminotetralins UH232 and AJ76 have been reported to be selective D2-like autoreceptor antagonists but these compounds also exhibit activity at D3 receptors where UH232 acts as a partial agonist.
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