Item


Side-effects of analgesic kyotorphin derivatives: advantages over clinical opioid drugs

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-NH 2 as advantageous alternatives over current opioids

© Amino Acids, 2013, vol. 45, p. 171-178

Springer Verlag

Author: Ribeiro, Marta M B
Santos, Sónia Sá
Sousa, David S C
Oliveira, Margarida
Santos, Sara Matos
Heras i Corominas, Montserrat
Bardají Rodríguez, Eduard
Tavares, Isaura R.
Castanho, Miguel Augusto Rico Botas
Date: 2013 July 1
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-NH 2 as advantageous alternatives over current opioids
Format: application/pdf
ISSN: 0939-4451 (versió paper)
1438-2199 (versió electrònica)
Document access: http://hdl.handle.net/10256/10175
Language: eng
Publisher: Springer Verlag
Collection: Reproducció digital del document publicat a: http://dx.doi.org/10.1007/s00726-013-1484-2
Articles publicats (D-Q)
info:eu-repo/grantAgreement/EC/FP7/230654
Is part of: © Amino Acids, 2013, vol. 45, p. 171-178
Rights: Tots els drets reservats
Subject: Pèptids
Peptides
Analgèsics
Analgesics
Title: Side-effects of analgesic kyotorphin derivatives: advantages over clinical opioid drugs
Type: info:eu-repo/semantics/article
Repository: DUGiDocs

Subjects

Authors