Synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain rats
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-ylphenyl-acetate] and tramadol in two neuropathy models, as well as their possible toxic effects, was analyzed. The anti-allodynic effect of PhAR-DBH...
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| Language: | English |
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2022-12-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2022-0037 |
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| author | Quiñonez-Bastidas Geovanna Nallely Osuna-Martínez Ulises Reda-Licea Ana Laura López-Ortíz Manuel Regla Ignacio Navarrete Andrés |
| author_facet | Quiñonez-Bastidas Geovanna Nallely Osuna-Martínez Ulises Reda-Licea Ana Laura López-Ortíz Manuel Regla Ignacio Navarrete Andrés |
| author_sort | Quiñonez-Bastidas Geovanna Nallely |
| collection | DOAJ |
| description | 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-ylphenyl-acetate] and tramadol in two neuropathy models, as well as their possible toxic effects, was analyzed. The anti-allodynic effect of PhAR-DBH-Me, tramadol, or their combination, were evaluated in neuropathic rats. Furthermore, the effective dose 35 (as the 35 % of the anti allodynic 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. |
| format | Article |
| id | doaj-art-870d37165d3542dcad6c776e19570b36 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-870d37165d3542dcad6c776e19570b362025-02-02T14:23:17ZengSciendoActa Pharmaceutica1846-95582022-12-0172450952710.2478/acph-2022-0037Synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain ratsQuiñonez-Bastidas Geovanna Nallely0Osuna-Martínez Ulises1Reda-Licea Ana Laura2López-Ortíz Manuel3Regla Ignacio4Navarrete Andrés5Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad Universitaria Coyoacán, Ciudad de México, MéxicoFacultad 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, 80010MexicoFacultad 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, 80010MexicoFacultad de Estudios Superiores Zaragoza Universidad Nacional Autónoma de México (UNAM), México, D.F., MéxicoFacultad de Estudios Superiores Zaragoza Universidad Nacional Autónoma de México (UNAM), México, D.F., MéxicoFacultad de Estudios Superiores Zaragoza Universidad Nacional Autónoma de México (UNAM), México, D.F., MéxicoIn 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-ylphenyl-acetate] and tramadol in two neuropathy models, as well as their possible toxic effects, was analyzed. The anti-allodynic effect of PhAR-DBH-Me, tramadol, or their combination, were evaluated in neuropathic rats. Furthermore, the effective dose 35 (as the 35 % of the anti allodynic 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.https://doi.org/10.2478/acph-2022-0037cannabinoid receptorsphar-dbh-metramadolsynergismantiallodynic effect |
| spellingShingle | Quiñonez-Bastidas Geovanna Nallely Osuna-Martínez Ulises Reda-Licea Ana Laura López-Ortíz Manuel Regla Ignacio Navarrete Andrés Synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain rats Acta Pharmaceutica cannabinoid receptors phar-dbh-me tramadol synergism antiallodynic effect |
| title | Synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain rats |
| title_full | Synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain rats |
| title_fullStr | Synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain rats |
| title_full_unstemmed | Synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain rats |
| title_short | Synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain rats |
| title_sort | synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain rats |
| topic | cannabinoid receptors phar-dbh-me tramadol synergism antiallodynic effect |
| url | https://doi.org/10.2478/acph-2022-0037 |
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