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. Author manuscript; available in PMC: 2013 Feb 28.
Published in final edited form as: Adv Exp Med Biol. 2012;740:603–638. doi: 10.1007/978-94-007-2888-2_27

Figure 2. Therapeutic approaches aimed at rescuing the brain α7 nAChR activation.

Figure 2

The left most pathway: ACh esterase inhibitors (e.g., donepezil) increase the CSF level of ACh and promote activation of both nAChRs and mAChRs. Despite cognitive benefits (dashed line), the lack of selectivity may cause considerable side effects (e.g., autonomic). The right most pathway: α7 nAChR agonists. A moderate activation of α7 nAChRs by selective agonists (e.g., DMXBA) protects neurons, benefits cognition and appears to be clinically safe. The middle pathway: positive allosteric modulators (PAMs) of α7 nAChRs. Choline is a low-potency endogenous selective agonist of α7 nAChRs, but its potency can be considerably increased by Type-II α7-PAMs, such as PNU-120596. α7-PAMs do not activate α7 nAChRs in the absence of nicotinic agonists. Instead, α7-PAMs lower the energy barrier, allowing lower concentrations of nicotinic agonists to activate the receptor. In the presence of Type-II α7-PAMs, endogenous choline may become effective in producing moderate persistent activation of native α7 nAChRs. This type of activation of α7 nAChRs may promote neuroprotection and benefit cognition.