1 2 propanediol 1 3 propanediol and racemic 1 3 butanediol were purchased from sigma aldrich co ethanol n propanol isopropyl alcohol and racemic 1 2 propanediol were obtained from local sources the cooling agents selected for testing were u2212 menthol ws 3 ws 5 1r 2s 5r 2 isopropyl 5 methyl cyclohexanecarbonyl amino acetic acid ethyl ester cps 147 cps 148 cps 368 r 2 1r 2s 5r 2 isopropyl 5 methyl cyclohexanecarbonyl amino propionic acid methyl ester cps 369 r 2 1r 2s 5r 2 isopropyl 5 methyl cyclohexanecarbonyl amino propionic acid ethyl ester cps 410 r 2 1r 2s 5r 2 isopropyl 5 methyl cyclohexanecarbonyl amino propionic acid n propyl ester and cps 412 r 2 1r 2s 5r 2 isopropyl 5 methyl cyclohexanecarbonyl amino propionic acid n butyl ester these compounds and their methods of synthesis are described in us 2008 0227857 a1 sep 18 2008 and in m b u00f6dding et al characterisation of trpm8 as a pharmacophore receptor cell calcium 2007 vol 42 618 28 incorporated herein by reference for assays on the skin the cooling agent s was dissolved in the alcoholic solvent to yield a 2 2 5 3 5 or 10 mg ml solution using a cotton tipped applicator e g q tips u00ae 0 10 to 0 25 ml of the test solution was applied to the skin above the upper lip on the philtrum and lateral to the philtrum up to the nasolabial folds and the onset and duration of cooling sensations noted the intensity of the subjective skin sensation was rated as 0 1 2 or 3 with 0 as no change 1 as slight coolness cold or tingling 2 as clear cut.