Analgesic activity of new 1,4-dihydropyridine-2-thiols containing a benzocaine fragment

Experiment was run on ninety white mongrel male rats weighing 220-250 g. Rats were divided into control (with orofacial trigeminal pain modelling by subcutaneous injection of 0.1 ml 5% formaldehyde solution in the vibrissae area), reference (which received metamizole sodium at a dose of 7 mg/kg) and seven test groups (received 1,4-dihydropyridine-2-thiols at a dose of 5 mg/kg intragastrically 1.5 hours prior to administration of algogenic substance) of ten animals each. Quantitative description is the number of orofacial scratching movements (NSM) per minute. Measurements were made 10, 15, 20 minutes after the algogenic substance administration.

In control group average NSMs were 90.2, 65.2, 35.2 after 10, 15, 20 minutes respectively. Animals were restless, scratching skin to scrapes. Metamizole sodium administration reduced NSM to 60, 37.6, 19.7 respectively. Mar-033 sample gave similar results; mar-035, mar-037 in the 10^th and 15^th minutes gave activity similar to metamizole sodium, in the 20th minute NSMs were 7.6 and 7.5 respectively; mar-040 after 10, 15, 20 minutes reduced NSMs to 36.2, 13.4, 5.3 respectively; mar-014 to 26.4, 6.6, 2; mar-075, mar-036 drastically reduced NSMs to 8.6 and 7.3 at the beginning of observation, to 6.6 and 3.3 respectively after 15 minutes and to 1 and less after 20 minutes.

Research showed that three substances had the maximum analgesic activity: mar-036 (ethyl 4-{[6-({2-[(4-butylphenyl)amino]-2-oxoethyl}thio)-5-cyano-4-(2-furyl)-2-methyl-1,4-dihydropyridin-3-yl)carbonyl}amino}benzoate), mar-075 (ethyl-4-{[(5-cyano-4-(2-furyl)-6-{[2-(4-methoxyphenyl)-2-oxoethyl]thio}-2-methyl-1,4-dihydropyridin-3-yl)carbonyl]amino}benzoate) were 19.7 times; mar-014 (ethyl-4-{[5-cyano-6-({2-[(3,5-dichlorophenyl)amino]-2-oxoethyl}thio)-4-(2-furyl)-2-methyl-1,4-dihydropyridin-3-yl)carbonyl]amino}benzoate) was 9.8 times more efficient than metamizole sodium.