mannich-bases and Pain

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2; Drug Design; Edema; Humans; Male; Mannich Bases; Mice, Inbred BALB C; Molecular Docking Simulation; Naproxen; Pain; Triazoles

Topics: Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Imidazolidines; Mannich Bases; Mice; Molecular Structure; Oxaliplatin; Pain; Rats; Seizures; Structure-Activity Relationship

The aim of the present experiments was to examine anticonvulsant activity of new pyrrolidine-2,5-dione and 3-methylpyrrolidine-2,5-dione derivatives in animal models of epilepsy. In addition, the possible collateral antinociceptive activity was assessed. Anticonvulsant activity was investigated in the electroconvulsive threshold (MEST) test and the pilocarpine-induced seizure models in mice. Antinociceptive activity was examined in the hot plate and the formalin tests in mice. Considering the drug safety evaluation, the Vibrio harveyi test was used to estimate anti/mutagenic activity. To determine the plausible mechanism of anticonvulsant action, for two chosen compounds (12 and 23), in vitro binding assays were carried out. All of the tested compounds revealed significant anticonvulsant activity in the MEST test. Compounds 12 and 23 displayed anticonvulsant effect also in pilocarpine-induced seizures. Four of the tested compounds (12, 13, 15, and 24) revealed analgesic activity in the hot plate test as well as in the first phase of the formalin test, and all of them were active in the second phase of the formalin test. The possible mechanism of action of compounds 12 and 23 is the influence on the neuronal voltage-sensitive sodium and L-type calcium channels. The obtained results indicate that in the group of pyrrolidine-2,5-diones, new anticonvulsants with collateral analgesic properties can be found.

Topics: Analgesics; Animals; Anticonvulsants; Calcium Channels, L-Type; Formaldehyde; Hot Temperature; Male; Mannich Bases; Mice; Motor Activity; Mutagenicity Tests; Pain; Pilocarpine; Seizures; Sodium Channels; Succinimides; Vibrio

Mannich bases were selected for 2D QSAR study to derive meaningful relationship between the structural features and analgesic activity. Using the knowledge of important features a novel series was designed to obtain improved analgesic activity. A series of novel Mannich bases 1-(N-substituted amino)methyl]-2-substituted benzimidazole derivatives were synthesized and were screened for analgesic activity. Some of these compounds showed promising analgesic activity when compared with the standard drug diclofenac sodium.

Topics: Acetic Acid; Analgesics; Animals; Benzimidazoles; Diclofenac; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Humans; Hyperkinesis; Inflammation; Male; Mannich Bases; Mice; Pain; Structure-Activity Relationship

In continuation of structure activity relationship studies, a panel of fluorine containing sydnones with styryl ketone group 4-[1-oxo-3-(substituted aryl)-2-propenyl]-3-(3-chloro-4-fluorophenyl)sydnones 2a-i, was synthesized as better analgesic and anti-inflammatory agents. The title compounds were formed by condensing 4-acetyl-3-(3-chloro-4-fluorophenyl)sydnone with various substituted aryl aldehydes, characterized by spectral studies and evaluated at 100 mg\\kg b.w., p.o. for analgesic, anti-inflammatory and ulcerogenic activities. Compounds 2c and 2e showed good analgesic effect in acetic acid-induced writhing while none showed significant activity in hot plate assay in mice. In carrageenan-induced rat paw oedema test, compound 2c and 2f exhibited good anti-inflammatory effect at 3rd h, whereas compounds 2c, 2e, 2d, 2g and 2h showed activity in croton oil induced ear oedema assay in mice. Compounds 2c and 2e were less ulcerogenic than ibuprofen in rats, when tested by ulcer index method. Compounds with electron attracting substituents such as 2c and 2e were found to be promising in terms of the ratio of efficacy and adverse effect. These compounds generally exhibited better activity than those of earlier series signifying fluorine substitution.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Croton Oil; Edema; Female; Fluorine; Male; Mannich Bases; Mice; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Structure-Activity Relationship; Sydnones

A series of 4-[(4-aryl)methylidene]amino-2-(substituted-4-ylmethyl)-5-{1-[4-(2-methylpropyl)phenyl]ethyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione (6) were synthesized from an arylpropionic acid namely, ibuprofen by a three-component Mannich reaction. Aminomethylation of 4-[(4-aryl)methylidene]amino-5-{1-[4-(2-methylpropyl)phenyl] ethyl}-4H-1,2,4-triazole-3-thiol (5) with formaldehyde and a secondary amine furnished this novel series of Mannich bases (6). Both Schiff bases (5) and Mannich bases (6) were well characterized on the basis of IR, NMR, mass spectral data and elemental analysis. They were screened for their anti-inflammatory, analgesic, antibacterial and antifungal activities. Some of the Mannich bases (6) carrying morpholino and N-methylpiperazino residues were found to be promising anti-inflammatory and analgesic agents.

Topics: Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspergillus; Edema; Escherichia coli; Ibuprofen; Inflammation; Mannich Bases; Mice; Pain; Rats; Rats, Wistar; Schiff Bases; Staphylococcus aureus; Triazoles