title: Antinociceptive effect induced by a combination of opioid and neurotensin moieties vs. their hybrid peptide [Ile(9)]PK20 in an acute pain treatment in rodents.
abstract: Hybrid compounds are suggested to be a more effective remedy for treatment of various diseases than combination therapy, since the attenuation or total disappearance of side effects, typically induced by a single moiety, can be observed. This is of great importance, especially when we consider problems resulting from the use of opioid analgesics. However, although it seems that such compounds can be valuable therapeutic tools, the lack of conviction among the public as to the appropriateness of their use still remains; therefore patients are commonly treated with polypharmacy. Thus, in the presented paper we show a comparison of the antinociceptive effect between a novel opioid-neurotensin chimera called [Ile(9)]PK20 and a mixture of its structural elements, delivered intrathecally and systemically. Additionally, motor coordination was assessed in the rotarod test. The results clearly indicate that spinal administration of the examined compounds, resulted in a long-lasting, dose- and time-dependent antinociceptive effect. Although the mixture of both pharmacophores was found to be more active than [Ile(9)]PK20, motor impairments surfaced as a side effect. This in turn illustrates the advantageous use of hybrid structures over drug cocktails.
authors.affiliation: Department of Pharmacodynamics, Centre for Preclinical Research and Technology, Medical University of Warsaw, 1B Banacha Str., 02-097 Warsaw, Poland; Department of Neuropeptides, Medical Research Centre Polish Academy of Sciences, 5 Pawinskiego Str., 02-106 Warsaw, Poland. Electronic address: hazufiel@wp.pl.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Kleczkowska
authors.affiliation: Laboratory of Pharmacology, Université Catholique de Louvain, Avenue Hippocrate 54, B-1200 Brussels, Belgium.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hermans
authors.affiliation: Department of Neuropeptides, Medical Research Centre Polish Academy of Sciences, 5 Pawinskiego Str., 02-106 Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kosson
authors.affiliation: Department of Pharmacodynamics, Centre for Preclinical Research and Technology, Medical University of Warsaw, 1B Banacha Str., 02-097 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kowalczyk
authors.affiliation: Department of Neuropeptides, Medical Research Centre Polish Academy of Sciences, 5 Pawinskiego Str., 02-106 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lesniak
authors.affiliation: Department of Pharmacodynamics, Centre for Preclinical Research and Technology, Medical University of Warsaw, 1B Banacha Str., 02-097 Warsaw, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Pawlik
authors.affiliation: Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt 62, 6726 Szeged, Hungary.
authors.forename: Engin
authors.initials: E
authors.lastname: Bojnik
authors.affiliation: Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt 62, 6726 Szeged, Hungary.
authors.forename: Sandor
authors.initials: S
authors.lastname: Benyhe
authors.affiliation: Department of Neuropeptides, Medical Research Centre Polish Academy of Sciences, 5 Pawinskiego Str., 02-106 Warsaw, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nowicka
authors.affiliation: Department of Pharmacodynamics, Centre for Preclinical Research and Technology, Medical University of Warsaw, 1B Banacha Str., 02-097 Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bujalska-Zadrozny
authors.affiliation: Department of Neuropeptides, Medical Research Centre Polish Academy of Sciences, 5 Pawinskiego Str., 02-106 Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Misicka
authors.affiliation: Department of Neuropeptides, Medical Research Centre Polish Academy of Sciences, 5 Pawinskiego Str., 02-106 Warsaw, Poland.
authors.forename: Andrzej W
authors.initials: AW
authors.lastname: Lipkowski
mesh_terms: D059787:Acute Pain / Q000188:drug therapy*; D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D008297:Male; D009496:Neurotensin / Q000737:chemistry / Q000494:pharmacology; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy; D059408:Pain Management; D010147:Pain Measurement / Q000187:drug effects; D010455:Peptides / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D004338:Drug Combinations; D009842:Oligopeptides; C000616899:PK20 peptide; C000598338:PK20 peptide, Ile(9)-; D010455:Peptides; D009496:Neurotensin
keywords: Analgesia; Motor coordination assay; Opioid-neurotensin hybrid peptide; Tail-flick test