Original scientific paper

https://doi.org/10.2478/acph-2022-0037

Synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain rats

GEOVANNA NALLELY QUIÑONEZ-BASTIDAS ; Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, Ciudad de México, México
ULISES OSUNA-MARTÍNEZ ; Facultad de Ciencias Químico-Biológicas, Laboratorio de Investigación en Farmacia, Farmacobiología y Toxicobiología, Universidad Autónoma de Sinaloa, Av. de las Américas y Boulevard Universitarios, Culiacán, Sinaloa, 80010, Mexico
ANA LAURA REDA-LICEA ; Facultad de Ciencias Químico-Biológicas, Laboratorio de Investigación en Farmacia, Farmacobiología y Toxicobiología, Universidad Autónoma de Sinaloa, Av. de las Américas y Boulevard Universitarios, Culiacán, Sinaloa, 80010, Mexico
MANUEL LÓPEZ-ORTÍZ orcid.org/0000-0002-6631-2619 ; Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México (UNAM), México, D.F., México
IGNACIO REGLA ; Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México (UNAM), México, D.F., México
ANDRÉS NAVARRETE orcid.org/0000-0002-2858-8710 ; Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, Ciudad de México, México; Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México (UNAM), México, D.F., México

Abstract

In the present study the interaction of cannabinoid, PhAR-DBH-Me [(R,Z)-18-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-18-oxooctadec-9-en-7-ylphenylacetate] and tramadol in two neuropathy models, as well as their possible toxic effects, was analyzed. The antiallodynic effect of PhAR-DBH-Me, tramadol, or their combination, were evaluated in neuropathic rats. Furthermore, the effective dose 35 (as the 35 % of the antiallodynic effect) was calculated from the maximum effect of each drug. Moreover, the isobolographic analysis was performed to determine the type of interaction between the drugs. A plasma acute toxicity study was carried out to assess the hepatic, renal, and heart functions after an individual or combined administration of the drugs, as well as histology using the hematoxylin-eosin or Masson-trichome method. PhAR-DBH-Me, tramadol, and their combination produced an antiallodynic effect on spinal nerve ligation (SNL) and cisplatin-induced neuropathic pain in rats. Moreover, PhAR-DBH-Me and tramadol combination showed a synergistic interaction in neuropathic pain rats induced by SNL but not for cisplatin-induced neuropathy. On the other hand, changes in renal and hepatic functions were not observed. Likewise, analysis of liver, kidney and heart histology showed no alterations compared with controls. Results show that the combination of PhAR-DBH-Me and tramadol attenuates the allodynia in SNL rats; the acute toxicology analysis suggests that this combination could be considered safe in administered doses.

Keywords

cannabinoid receptors; PhAR-DBH-Me; tramadol; synergism; antiallodynic effect

Hrčak ID:

278099

URI

https://hrcak.srce.hr/278099

Publication date:

31.12.2022.

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