PGI-7043 is aserotonin5-HT_1B and5-HT_1D receptoragonist.^[1] It is apotent and highlycentrallypenetrantfull agonist of the serotonin 5-HT_1B and 5-HT_1D receptors (EC₅₀Tooltip half-maximal effective concentration = 1.3 nM and 0.5 nM, respectively).^[1]

The drug producesantidepressant-like,antiaggressive, andprosocial effects in rodents without producingsedation.^[1] In contrast,zolmitriptan was only weakly effective at a 100-fold higher dose in terms of antidepressant-like effects.^[1] This may be related totriptans like zolmitriptan having limitedblood–brain barrier permeability and hence beingperipherally selective.^[1] Moreover, whileolanzapine also produced antiaggressive effects, it produced sedation and reducedsocial interaction as well.^[1] PGI-7043 suppressedrapid eye movement (REM)sleep as measured withelectroencephalography (EEG) in rodents, which could serve as a novel translationalbiomarker forclinical studies.^[1] Serotonin 5-HT_1B and 5-HT_1D receptoroccupancy were confirmed in rodents at doses producing behavioral and EEG effects.^[1] The drug is described as having excellentdrug-like properties.^[1]

PGI-7043 was first described in thescientific literature in December 2024.^[1] It was discovered by PsychoGenics using their SmartCubedrug discovery platform following screening of approximately 300 compounds.^[1] The drug might have therapeutic applications in the treatment of conditions likeagitation inAlzheimer's disease,bipolar disorder, andschizophrenia as well as treatment of reducedsocial behavior inautism spectrum disorders.^[1] Itschemical structure does not yet appear to have been disclosed.^[1]

• Serotonin 5-HT_1B receptor agonist
• Serenic (antiaggressive drug)
• List of investigational aggression drugs
• List of investigational agitation drugs
• List of investigational autism and pervasive developmental disorder drugs
• Zolmitriptan § Social deficits and aggression

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