生物活性

• 描述The activation of brain α7 nicotinic acetylcholine receptors (α7 nAChRs) is involved in central nervous system disease related to cognitive dysfunction. CCMI is a positive allosteric modulator of α7 nAChRs. It dose-dependently evoked positive modulation of EC₅ currents induced by acetylcholine, choline, and nicotine with EC₅₀ values of 0.7 ± 0.2 μM, 0.6 ± 0.1 μM, and 0.5 ± 0.1 μM, respectively, and with n_H values of 1.4 ± 0.9, 1.2 ± 0.3, and 1.2 ± 0.3, respectively. CCMI at 1 μM induced a leftward shift in the concentration-response curve for acetylcholine, leading to a 2.7-fold reduction in the EC₅₀ value for acetylcholine compared to the group without CCMI. In oocytes, CCMI evoked positive modulation of submaximal GABA-evoked currents at human GABA_A α1β2γ2L receptors with an EC₅₀ value of 6.3 ± 0.2 μM. It also evoked positive modulation of choline-evoked currents in SH-SY5Y cells transfected with α7 nAChRs (a 1.8-fold increase compared to control). In the DBA/2 mouse model of sensory-gating deficit, intravenous administration of CCMI at the dosages of 0.3 and 1 mg/kg significantly reduced the ratio of test amplitude to conditioning amplitude up to 90 min after administration. In NSA mice, oral administration of CCMI at 0.3 - 3 mg/kg significantly reversed MK-801-induced hyperlocomotion^[1].

• 动物研究
  剂量	Mice: 0.1 mg/kg - 1 mg/kg[1] (i.p.) Rat: 0.3 mg/kg - 3 mg/kg[2] (i.p.)
  给药途径	i.p.