Publication
Side-effects of analgesic kyotorphin derivatives : advantages over clinical opioid drugs
| dc.contributor.author | Ribeiro, Marta M. B. | |
| dc.contributor.author | Santos, Sónia Sá | |
| dc.contributor.author | Sousa, David S. C. | |
| dc.contributor.author | Oliveira, Margarida | |
| dc.contributor.author | Santos, Sara M. | |
| dc.contributor.author | Heras, Montserrat | |
| dc.contributor.author | Bardaji, Eduard | |
| dc.contributor.author | Tavares, Isaura | |
| dc.contributor.author | Castanho, Miguel A. R. B. | |
| dc.date.accessioned | 2014-03-05T16:55:58Z | |
| dc.date.available | 2014-03-05T16:55:58Z | |
| dc.date.issued | 2013 | |
| dc.description | © Springer-Verlag 2013 | eng |
| dc.description.abstract | The adverse side-effects associated with opioid administration restrain their use as analgesic drugs and call for new solutions to treat pain. Two kyotorphin derivatives, kyotorphin-amide (KTP–NH2) and ibuprofen–KTP–NH2 (IbKTP–NH2) are promising alternatives to opioids: they trigger analgesia via an indirect opioid mechanism and are highly effective in several pain models following systemic delivery. In vivo side-effects of KTP–NH2 and IbKTP–NH2 are, however, unknown and were evaluated in the present study using male adult Wistar rats. For comparison purposes, morphine and tramadol, two clinically relevant opioids, were also studied. Results showed that KTP-derivatives do not cause constipation after systemic administration, in contrast to morphine. Also, no alterations were observed in blood pressure or in food and water intake, which were only affected by tramadol. A reduction in micturition was detected after KTP–NH2 or tramadol administrations. A moderate locomotion decline was detected after IbKTP–NH2-treatment. The side-effect profile of KTP–NH2 and IbKTP–NH2 support the existence of opioid-based mechanisms in their analgesic actions. The conjugation of a strong analgesic activity with the absence of the major side-effects associated to opioids highlights the potential of both KTP–NH2 and IbKTP–NH2 as advantageous alternatives over current opioids. | eng |
| dc.description.sponsorship | Fundação para a Ciência e Tecnologia (Portugal) is acknowledged for funding: SFRH/BD/42158/2007 fellowship to M. Ribeiro and SFRH/BI/51213/2010 fellowship (for doctorate) to S. Sá Santos associated to Marie Curie IAPP. Marie Curie Industry-Academia Partnerships and Pathways (European Commission) is also acknowledged for funding (FP7-PEOPLE-2007-3-1-IAPP. Project 230654). The authors acknowledge and appreciate the financial support received from Faculdade de Medicina da Universidade de Lisboa and Fundação Amadeu Dias, Portugal (Project No. 2010029) | eng |
| dc.identifier.citation | Amino Acids (2013) 45:171–178 | eng |
| dc.identifier.issn | 0939-4451 | |
| dc.identifier.uri | http://dx.doi.org/10.1007/s00726-013-1484-2 | |
| dc.identifier.uri | http://hdl.handle.net/10451/10689 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | Springer | eng |
| dc.relation.publisherversion | The definitive version is available at http://www.springer.com/ | eng |
| dc.subject | Kyotorphin | eng |
| dc.subject | Analgesic peptides | eng |
| dc.subject | Opioids | eng |
| dc.subject | Side-effects | eng |
| dc.subject | Morphine | eng |
| dc.subject | Constipation | eng |
| dc.title | Side-effects of analgesic kyotorphin derivatives : advantages over clinical opioid drugs | eng |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.awardURI | info:eu-repo/grantAgreement/EC/FP7/230654 | |
| oaire.citation.endPage | 178 | por |
| oaire.citation.startPage | 171 | por |
| oaire.citation.title | Amino Acids | eng |
| oaire.citation.volume | 45 | por |
| oaire.fundingStream | FP7 | |
| project.funder.identifier | http://doi.org/10.13039/501100008530 | |
| project.funder.name | European Commission | |
| rcaap.rights | closedAccess | por |
| rcaap.type | article | por |
| relation.isProjectOfPublication | c0d24731-bdbf-43ff-a9ae-fe6ad95c2622 | |
| relation.isProjectOfPublication.latestForDiscovery | c0d24731-bdbf-43ff-a9ae-fe6ad95c2622 |