Wrinkles can have a negative effect on quality of life and Botox is one of the most effective and common treatments. Argireline (Arg0), a mimetic of Botox, has been found to be safer than Botox and effective in reducing wrinkles, with efficacies up to 48% upon 4 weeks of twice daily treatment. However, the skin permeation of Arg0 is poor, due to its large molecular weight and hydrophilicity. Arg0 exists in zwitterionic form and this charged state hindered its skin permeation. Chemical modification of the peptide structure to reduce the formation of zwitterions may result in increased skin permeability. We investigated a total of 4 peptide analogues (Arg0, Arg1, Arg2, Arg3), in terms of skin permeation and wrinkle reduction. The 4 peptides were dissolved in various propylene glycol and water co-solvents. Enhanced human skin permeation was demonstrated by both Arg2 and Arg3 in vitro. On the other hand, the abilities of the 4 analogues to reduce wrinkle formation were also compared using primary human dental pulp stem cells derived neurons. By measuring the inhibition of glutamate release from the neurons in vitro, it was shown that Arg3 was the most effective, followed by Arg1, Arg0 and Arg2.