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Ghelardini, C. et al.

Ghelardini, Mizuma, Gualtieri, Bartolini, Galeotti, Romanelli, Teodori,

Binding profiles of a series of 2-arylpropionic acid esters on cloned human muscarinic receptor subtypes (m1-m5) and their relationship to nootropic activity.

The muscarinic binding profile of a series of 2-arylpropionic acid esters on cloned human muscarinic receptor subtypes (m1-m5) was determined to investigate whether there is a correlation between pharmacological activity and muscarinic receptor subtype selectivity. Among the tested compounds, 1, 7 and 9 showed the highest affinity for the m2 and m4 receptors. Compounds 1, 7 and 9 show good affinity for m4 receptors (pKi = 7.87; 7.73 and 7.10, respectively) and are able to discriminate 10-60 fold between m4/m1, m4/m3, and m4/ m5 subtypes. Conversely, these compounds are able only to weakly discriminate between m4/m2. Compounds 1 (50-300 micrograms kg-1 i.p.) and 7 (1-10 micrograms kg-1 i.p.), injected 20 min before the training session, are able to prevent the amnesia induced by dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Compounds 1 and 7, at the highest antiamnesic doses, do not modify motor coordination and spontaneous motility as evaluated by the rota-rod test and Animex apparatus experiments.[1]

References

Binding profiles of a series of 2-arylpropionic acid esters on cloned human muscarinic receptor subtypes (m1-m5) and their relationship to nootropic activity. Ghelardini, C., Mizuma, I., Gualtieri, F., Bartolini, A., Galeotti, N., Romanelli, M.N., Teodori, E. Arzneimittel-Forschung. (1999) [Pubmed]

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