A novel cinnamic and caffeic acid-conjugated peptide analogs with anticonvulsant and analgesic potency: Comparative analyses of trans/cis isomers.
analgesic potency
antiseizure activity
cinnamic and caffeic acid‐hemorphin derivates
mice
opioid receptors
Journal
Drug development research
ISSN: 1098-2299
Titre abrégé: Drug Dev Res
Pays: United States
ID NLM: 8204468
Informations de publication
Date de publication:
Aug 2024
Aug 2024
Historique:
revised:
25
06
2024
received:
21
04
2024
accepted:
09
07
2024
medline:
20
7
2024
pubmed:
20
7
2024
entrez:
20
7
2024
Statut:
ppublish
Résumé
The novel cinnamic acid (CA) (H4-CA, H5-CA, and H7-CA) and caffeic acid (KA) (H4-KA, H5-KA, and H7-KA) hemorphin analogs have recently been synthesized and their trans isomers have been tested for antiseizure and antinociceptive activity. In the present study, the cis forms of these compounds were tested and compared with their trans isomers in seizure and nociception tests in mice. The cis-H5-CA and H7-CA compounds showed efficacy against psychomotor seizures, whereas the trans isomers were ineffective. Both the cis and trans KA isomers were ineffective in the 6-Hz test. In the maximal electroshock (MES) test, the cis isomers showed superior antiseizure activity to the trans forms of CA and KA conjugates, respectively. The suppression of seizure propagation by cis-H5-CA and the cis-H5-KA was reversed by a kappa opioid receptor (KOR) antagonist. Naloxone and naltrindole were not effective. The cis-isomers of CA conjugates and cis-H7-KA produced significantly stronger antinociceptive effects than their trans-isomers. The cis-H5-CA antinociception was blocked by naloxone in the acute phase and by naloxone and KOR antagonists in the inflammatory phase of the formalin test. The antinociception of the KA conjugates was not abolished by opioid receptor blockade. None of the tested conjugates affected the thermal nociceptive threshold. The results of the docking analysis also suggest a model-specific mechanism related to the activity of the cis-isomers of CA and KA conjugates in relation to opioid receptors. Our findings pave the way for the further development of novel opioid-related antiseizure and antinociceptive therapeutics.
Substances chimiques
Analgesics
0
Anticonvulsants
0
Cinnamates
0
Caffeic Acids
0
cinnamic acid
140-10-3
caffeic acid
U2S3A33KVM
Peptides
0
Types de publication
Journal Article
Comparative Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22236Subventions
Organisme : The European Union-Next Generation EU
Organisme : project No. BG-RRP-2.004-0002, "BiOrgaMCT"
Organisme : Through the National Recovery and Resilience Plan of the Republic of Bulgaria
Informations de copyright
© 2024 Wiley Periodicals LLC.
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