5-Iodo-A-85380 (dihydrochloride)

5-Iodo-A-85380 dihydrochloride (5-I A-85380 dihydrochloride) is a blood-brain barrier-permeable selective ligand for α4β2 nicotinic acetylcholine receptors (nAChR). The K_i of 5-Iodo-A-85380 dihydrochloride binding to rat α4β2 nAChRs is 0.01 nM. 5-Iodo-A-85380 dihydrochloride activates receptor currents, elicits single-channel currents, and promotes calcium influx, dopamine release, and calcium-dependent neuroprotection, acting as a full agonist at high-sensitivity α4β2 and a partial agonist at low-sensitivity α4β2 and α6-containing nAChRs. 5-Iodo-A-85380 dihydrochloride can be used for research on glutamate-induced neurotoxicity, pain, Alzheimer's disease, Parkinson's disease, schizophrenia, and attention deficit hyperactivity disorder^{[1][2][3][4][5][6][7][8]}. In Vitro:5-Iodo-A-85380 (10-100 nM) dihydrochloride produces a single-channel conductance of 17 pS in HEK293 cells stably expressing human α4β2 nicotinic receptors^[1].
5-Iodo-A-85380 (1.5 h or 3 h) dihydrochloride exhibits extremely high selectivity for α4β2 nAChRs (K_i = 0.010 nM), with 5,000- to 140,000-fold lower affinity for α3β4x, α7, and muscle-type nAChRs^[3].
5-Iodo-A-85380 dihydrochloride potently activates expressed human α4 (2)β2 (3), α4 (3)β2 (2), and β3α4β2α6β2 nAChRs in Xenopus oocytes, with peak current EC₅₀ values of 42, 37, and 11 nM, respectively, acting as a full agonist at HS α4 (2)β2 (3)^[4].
5-Iodo-A-85380 dihydrochloride induces [³H]dopamine release sensitive to DHbE in rat striatum and PFC prisms, with pEC₅₀ values of 7.9 and 8.1, respectively^[8].
5-Iodo-A-85380 (0.1-1000 nM; 2 h) dihydrochloride (5-I A-85380 dihydrochloride) protects primary cultures of rat cortical neurons against glutamate-induced neurotoxicity, acting through α4β2 nAChRs and requiring extracellular Ca^2+[2]. In Vivo:5-Iodo-A-85380 (5IA) (0.01-1 mg/kg; subcutaneous injection; single acute injection) dihydrochloride (5-I A-85380 dihydrochloride) dose-dependently inhibits locomotor activity, and this inhibition requires the β2 nicotinic receptor subunit^[4].
5-Iodo-A-85380 (0.01-1 mg/kg; subcutaneous injection; once daily; for 5 consecutive days; followed by challenge on day 8) dihydrochloride produces dose- and time-dependent locomotor effects, but no locomotor sensitization occurs upon challenge on day 8^[4].
5-Iodo-A-85380 (0.01-0.5 mg/kg; subcutaneous injection; single injection) dihydrochloride induces time- and dose-dependent hypothermia in mice, and this effect is mediated by the β2 nicotinic receptor subunit^[4].
5-Iodo-A-85380 (A-85380) (0.18-0.75 μmol/kg/day; intraperitoneal injection; twice daily at 8-hour intervals; for 4 consecutive days) dihydrochloride reduces L-DOPA (HY-N0304)-induced AIMs by only about 20% in rats with nearly complete striatal dopamine lesions^[7].
5-Iodo-A-85380 (0.37 μmol/kg/day; intraperitoneal injection; twice daily at 8-hour intervals; for 4 consecutive days) dihydrochloride reduces L-DOPA-induced AIMs by approximately 50% in rats with partial striatal dopamine lesions without exacerbating the anti-parkinsonian response to L-DOPA^[7].
5-I-A-85380 (100 µM-1 mM) dihydrochloride locally perfused into the medial prefrontal cortex increases extracellular dopamine overflow in awake, freely moving rats^[8].