(+)-Dihydrexidine (hydrochloride)

(+)-Dihydrexidine hydrochloride ((+)-DAR-0100 hydrochloride) is a dopamine D1 receptor agonist with an EC₅₀ of 72± 21 nM. IC50 & Target: EC50: 72±21 nM (Dopamine D1 receptor)^[1] In Vitro: (+)-Dihydrexidine hydrochloride (DHX) is a high-potency, bioavailable D1 dopamine receptor agonist. (+)-Dihydrexidine is screened for activity against 40 other binding sites, and is inactive (IC₅₀ greater than 10 microM) against all except D2 dopamine receptors (IC₅₀=130 nM) and alpha 2 adrenoreceptors (IC₅₀=230 nM). Dihydrexidine competes stereoselectively and potently for D1 binding sites in rat striatal membranes labeled with [³H]SCH23390 with an IC₅₀ of about 10 nM compared to about 30 nM for the prototypical D1 agonist SKF38393^[2]. In Vivo: To examine the functional state of striatal neurons in response to D1 receptor activation, AC5^+/+ and AC5^-/- mice are injected with the D1 agonist (+)-Dihydrexidine (30 mg/kg, i.p.) and obtained the dorso-lateral striatum and NAc, separately, 45 min later for RT-PCR analysis. These experiments reveal that (+)-Dihydrexidine -triggered induction of the immediate early genes, c-fos, egr-1, and junB, in the NAc is markedly enhanced in AC5^-/- mice compared with that in AC5^+/+ mice, while the induction in the dorso-lateral striatum is suppressed in AC5^-/- mice^[3].