Today, despite numerous analgesic drugs available, many pain syndromes are still unsatisfactorily treated. For this reason great number of the N-aminoalkyl derivatives of 3,4-pyridinedicarboximides were synthesized by H. Śladowska’s research group, because  our previous investigations revealed significant analgesic activity of that chemical  group. Some of them were tested in a pharmacological screening test and they have shown both analgesic and sedative activities and were non-toxic (LD₅₀> 2000 mg/ kg) [1-4]. In order to obtain further information concerning structure-activity relationships (SAR)  in this  group of  compounds we modified the structure of 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones  by shortening of the side–alkyl chain. We obtained several new Mannich base type compounds. In the “writhing syndrome” test  all of the studied imides exhibited strong analgesic activity (ED₅₀ 1-4 = 0,72-2,82 mg/kg), which was superior to that of ASA (ED₅₀  = 39,15 mg/ kg). Imides 2 and 3 were more potent  than  morphine (ED₅₀ =2,44 mg/kg). In the “hot plate“ test all of the abovementioned derivatives showed potent analgesic activity. Furthermore, two compounds tested (3,4) significantly suppressed the spontaneous locomotor activity of mice but two (1,2) increased this activity in mice, acting like stimulants. It may suggested that the analgesic properties of these imides are not  consequences of their sedative activity, but the explanation of a precise mechanism of action will demand further pharmacological investigations.

References:

1. H. Śladowska, D. Szkatuła, B. Filipek, D. Maciąg, J. Sapa, M. Zygmunt: Pharmazie 56 (2) 133-138, 2001

2. H. Śladowska, B. Filipek, D. Szkatuła, A. Sabiniarz, M. Kardasz, J. Potoczek, M. Sieklucka-Dziuba, G. Rajtar, Z. Kleinrok, T. Lis :   Farmaco 57, 897-908, 2002

3. H. Śladowska, B. Filipek, D. Szkatuła, J. Sapa, M. Bednarski, M. Ciołkowska: Farmaco 60, 53-59, 2005

4. H. Śladowska, A. Sabiniarz, D. Szkatuła, B. Filipek, J. Sapa: Acta Polon. Pharm.: 63 (4) 245-254, 2006

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