In vivo effects of the association of the psychoactive phenotiazine thioridazine on antitumor activity and hind limb paralysis induced by the native polypeptide crotamine.

In vivo effects of the association of the psychoactive phenotiazine thioridazine on antitumor activity and hind limb paralysis induced by the native polypeptide crotamine. Toxicon. 2020 Jul 01;: Authors: Porta LC, Campeiro JD, Papa GB, Oliveira EB, Godinho RO, Rodrigues T, Hayashi MAF Abstract Crotamine is a cationic polypeptide composed by 42 amino acid residues with several pharmacological and biological properties, including the selective ability to enter and kill actively proliferating tumour cells, which led us to propose its use as a theranostic agent for cancer therapy. At the moment, the improvement of crotamine antitumoral efficacy by association with chemotherapeutic adjuvants is envisioned. In the present work, we evaluated the association of crotamine with the antitumoral adjuvant phenotiazine thioridazine (THD). In spite of the clear efficacy of these both compounds as anticancer agents in long-term in vivo treatment of animal model bearing implanted xenograph melanoma tumor, the expected mutual potentiation of the antitumor effects was not observed here. Moreover, this association revealed for the first time the influence of THD on crotamine ability to trigger the hind limb paralysis in mice, and this discovery may represent the first report suggesting the potential involvement of the CNS in the action of this snake polypeptide on the skeletal muscle paralysis, which was classically believed to be essentially limited to...
Source: Toxicon - Category: Toxicology Authors: Tags: Toxicon Source Type: research