OBJECTIVES: Using the pentylenetetrazol (PTZ) discrimination assay, this study aims to investigate the effects of MG in responding to the PTZ stimulus and to assess the generalisation effects of withdrawal from MG to the PTZ stimulus.
METHODS: Rats (n = 20) were trained on a tandem (FR-10, VI-15) schedule of food reinforcement to press one lever after administration of the anxiogenic compound PTZ (16 mg/kg, i.p.) and an alternate lever after vehicle. Following acute tests, training was suspended, and rats were chronically treated with MG or morphine at 8-h intervals for 9 days and withdrawal was precipitated on the tenth day using naloxone (1 mg/kg, i.p.). The rats were tested for generalisation to PTZ at 2, 8 and 24 h after the last dose of MG or morphine administration.
RESULTS: Unlike morphine that produced dose-related PTZ-like stimulus, MG at 3, 10, 30 and 45 mg/kg doses showed no substitution to the PTZ discriminative stimulus. In contrast to morphine which produced a time-dependent generalisation to the PTZ stimulus, naloxone did not precipitate withdrawal effects in MG-treated rats as they selected the vehicle lever at three withdrawal time points.
CONCLUSION: These results demonstrate that MG produces a very different response to morphine withdrawal that is not associated with anxiogenic-like subjective symptoms. These characteristics of MG may provide further support for use as a novel pharmacotherapeutic intervention for managing opioid use disorder.
METHODS: The molecules were tested for anticonvulsive activity in Swiss albino mice via maximal electroshock seizure and subcutaneous pentylenetetrazole assays. The most potent molecule among the class was further assayed for its effect on behavioral and CNS depressant activity. The effect of the most potent compounds was also analyzed on various indices of oxidative stress and inflammation in mice.
RESULTS: The designed compounds showed significant anticonvulsive activity in mice revealing 7h as the most potent anticonvulsive agent. The most potent anticonvulsant molecule 7h further showed no behavioral alteration and considerable CNS depressant activity. It also reduces the level of oxidative stress and inflammation in the mice.
CONCLUSION: Our study demonstrated utility of pyrazole derivatives as anticonvulsants against epilepsy.