Polymorphism and Pharmacological Assessment of Carbamazepine.

Sá Filho, Alberto; Martins, Jose Luis Rodrigues; Costa, Rafael Fernandes; Pedrino, Gustavo Rodrigues; Duarte, Vitor Santos; Silva, Osmar Nascimento; Napolitano, Hamilton Barbosa; Fajemiroye, James Oluwagbamigbe

This work provides insight into carbamazepine polymorphs (Forms I, II, III, IV, and V), with reports on the cytoprotective, exploratory, motor, CNS-depressant, and anticonvulsant properties of carbamazepine (CBZ), carbamazepine formulation (CBZ-F), topiramate (TOP), oxcarbazepine (OXC), and diazepam (DZP) in mice. Structural analysis highlighted the significant difference in molecular conformations, which directly influence the physicochemical properties; and density functional theory description provided indications about CBZ reactivity and stability. In addition to neuron viability assessment in vitro, animals were treated orally with vehicle 10 mL/kg, as well as CBZ, CBZ-F, TOP, OXC, and DZP at the dose of 5 mg/kg and exposed to open-field, rotarod, barbiturate sleep induction and pentylenetetrazol (PTZ 70 mg/kg)-induced seizure. The involvement of GABAergic mechanisms in the activity of these drugs was evaluated with the intraperitoneal pretreatment of flumazenil (2 mg/kg). The CBZ, CBZ-F, and TOP mildly preserved neuronal viability. The CBZ-F and the reference AEDs potentiated barbiturate sleep, altered motor activities, and attenuated PTZ-induced convulsion. However, flumazenil pretreatment blocked these effects. Additional preclinical assessments could further establish the promising utility of CBZ-F in clinical settings while expanding the scope of AED formulations and designs.

MOLECULAR conformation; DENSITY functional theory; FLUMAZENIL; GENETIC polymorphisms; TOPIRAMATE; CARBAMAZEPINE

International Journal of Molecular Sciences, 2024, Vol 25, Issue 18, p9835

1661-6596

Academic Journal

10.3390/ijms25189835