Antinociceptive properties of N-Mannich bases derived from 3-substituted pyrrolidine-2,5-dione in the formalin model of persistent pain in mice

Abstract

The results of the research indicate that some of the investigated compounds reduced effectively either both phases of the test or were able to attenuate pain during only the acute or late phase of the formalin test. These properties, which are particularly strong in case of the compounds 1-3, 5, 6, 9 and 14, might be relevant for the development of novel analgesic-active compounds and their possible use in neuropathic pain syndromes.

Anticonvulsant and antinociceptive activity of new amides derived from 3-phenyl-2,5-dioxo-pyrrolidine-1-yl-acetic acid in mice

“…Male CD-1 mice weighing 18-24 g were used in the in vivo experiment (Obniska et al, , 2015bSałat et al, 2014). The animals were housed and fed in a laboratory kept at constant temperature of 2072°C, under standard conditions (12:12 h light-dark cycle, standard pellet diet, tap water).…”

“…The animals were housed and fed in a laboratory kept at constant temperature of 2072°C, under standard conditions (12:12 h light-dark cycle, standard pellet diet, tap water). The experimental groups consisted of four to ten animals (Laughlin et al, 2002;Obniska et al, 2015aObniska et al, , 2015bSałat et al, 2014), and all the animals were used only once. The experiments were performed between 8 AM and 3 PM.…”

“…a TPE -time to peak effect b ED 50 (MES -maximal electroshock seizure test) c ED 50 (scPTZ -pentylenetetrazole seizure test) d ED 50 (6 Hz, psychomotor seizure test) e TD 50 (NT -acute neurological toxicity determined in the rotarod test) f Protective index (TD 50 /ED 50 ) g Reference anticonvulsant drugs tested in the same conditions. Data from the previous studies (Kamiński et al, 2015a;Obniska et al, 2016Obniska et al, , 2015b. TPEs for model anticonvulsant drugs taken from literature (White et al, 2002).…”

“…Our previous research showed that some of the tested agents based on the core of pyrrolidino-2,5-dione revealed prominent anticonvulsant properties in 'classical' animal models of seizures, i.e., MES, scPTZ, as well as in the 6 Hz model of pharmacoresistant limbic seizures and displayed distinctly better safety profile than clinically relevant anticonvulsant drugs (Kamiński et al, 2015a;Obniska et al, 2015aObniska et al, , 2015bRapacz et al, 2016;Rybka et al, , 2015Rybka et al, , 2014. Moreover, several compounds demonstrated analgesic activity in the formalin model of tonic pain in mice (Obniska et al, , 2015bRapacz et al, 2016).…”

“…Moreover, several compounds demonstrated analgesic activity in the formalin model of tonic pain in mice (Obniska et al, , 2015bRapacz et al, 2016).…”