Recent advances in the development of dopamine D(3) receptor agonists and antagonists.
Advances in molecular cloning techniques have allowed the characterization of five subtypes (D(1)-D(5)) of dopamine (DA) receptors. The limbic location of the D(3) receptor has led to speculation about its possible role in schizophrenia and drug abuse. Since the D(3) receptor is localized in the limbic region rather than the striatum, antipsychotics with D(3) receptor selectivity could be devoid of extrapyramidal side effects commonly seen with D(2) receptor antagonists. Recent work in our laboratory revealed that the benz[e] indole cis-(+/-)-44b demonstrated high selectivity for the D(3) receptor. This compound exhibits a typical antipsychotic profile without the motor effects found in commonly used antipsychotic agents. This mini-review will give a brief introduction on D(3) receptors and a detailed description of selectively-acting D(3) agonists and antagonists which have recently appeared in the literature.
Crider
A M
AM
Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, 71209-0470, USA. pycrider@ulm.edu
Scheideler
M A
MA
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D008024:Ligands; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D050637:Receptors, Dopamine D3; D012559:Schizophrenia / Q000188:drug therapy; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; C493593:DRD3 protein, human; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D008024:Ligands; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3