in humans. The selective D1 agonists give profound antiparkinson effects in humans and primate models of PD, and yield cognitive enhancement in many preclinical models and a few clinical trials. The most dose-limiting feature is profound hypotension, but the clinical development was impeded largely by lack of oral bioavailability and short duration of action. In 2017, Pfizer made public information about pharmaceutically-acceptable non-catechol selective D1 agonists that are in clinical development. List of D1 receptor agonists Dihydrexidine derivatives A-86929 - full agonist with 14-fold selectivity for D1-like receptors over D2 Dihydrexidine - full agonist with 10-fold selectivity for D1-like receptors over D2 that has been in Phase IIa clinical trials as a cognitive enhancer. It also showed profound antiparkinson effects in MPTP-treated primates, but caused profound hypotension in one early clinical trial in Parkinson's disease. Although dihydrexidine has significant D2 properties, it is highly biased at D2 receptors and was used for the first demonstration of functional selectivity with dopamine receptors. Dinapsoline - full agonist with 5-fold selectivity for D1-like receptors over D2 Dinoxyline - full agonist with approximately equal affinity for D1-like and D2 receptors Doxanthrine - full agonist with 168-fold selectivity for D1-like receptors over D2 Benzazepine derivatives SKF-81297 - 200-fold selectivity for D1 over any other receptor SKF-82958 - 57-fold selectivity for D1 over D2 SKF-38393 - very high selectivity for D1 with negligible affinity for any other receptor Clozapine - partial agonist at D1-like receptors Fenoldopam - highly selective peripheral D1 receptor partial agonist used clinically as an antihypertensive 6-Br-APB - 90-fold selectivity for D1 over D2 Others Stepholidine - alkaloid with D1 agonist and D2 antagonist properties, showing antipsychotic effects A-68930 A-77636 CY-208,243 - high intrinsic activity partial agonist with moderate selectivity for D1-like over D2-like receptors, member of ergoline ligand family like pergolide and bromocriptine. SKF-89145 SKF-89626 7,8-Dihydroxy-5-phenyl-octahydrobenzo[h]isoquinoline: extremely potent, high-affinity full agonist Cabergoline - weak D1 agonism, highly selective for D2, and various serotonin receptors Pergolide - (similar to cabergoline) weak D1 agonism, highly selective for D2, and various serotonin receptors A photoswitchable agonist of D1-like receptors (azodopa) has been described that allows reversible control of dopaminergic transmission in wildtype animals. Antagonists Many typical and atypical antipsychotics are D1 receptor antagonists in addition to D2 receptor antagonists. But Asenapine has shown stronger D1 receptor affinity compared to other antipsychotics. No other D1 receptor antagonists have been approved for clinical use. Ecopipam is a