Palladium-benzodiazepine derivatives as promising metallodrugs for the development of antiepileptic therapies.

Palladium-benzodiazepine derivatives as promising metallodrugs for the development of antiepileptic therapies. J Inorg Biochem. 2015 Dec 2;155:129-135 Authors: Barros WB, da Silva AH, Barbosa AS, Nunes ÁM, Reys JR, de Araújo-Filho HG, de Souza Siqueira Quintans J, Quintans-Júnior LJ, Pfeffer M, Dos Santos Malta VR, Meneghetti MR Abstract We synthesized two organometallic diazepam-palladium(II) derivatives by C-H activation of diazepam (DZP) with palladium salts, i.e., PdCl2 and Pd(OAc)2 (OAc=acetate). Both compounds obtained are air stable and were isolated in good yields. The anticonvulsant potential of the complexes, labeled [(DZP)PdCl]2 and [(DZP)PdOAc]2, was evaluated through two animal models: pentylenetetrazole (PTZ)- and picrotoxin (PTX)-induced convulsions. The organometallic DZP-palladium(II) acetate complex, [(DZP)PdOAc]2, significantly increased (p<0.01 or p<0.001) latencies and protected the animals against convulsions induced by PTZ and PTX, while the analogous chloro derivative, [(DZP)PdCl]2, was effective (p<0.01) only in the PTZ model. These effects appear to be mediated through the GABAergic system. The possible mechanism of action of the DZP-palladium(II) complexes was also confirmed with the use of flumazenil (FLU), a GABAA-benzodiazepine receptor complex site antagonist. Herein, we present the first report of the anticonvulsant properties of organometallic DZP-palladium(II) complexes as well as evidenc...
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research