Research reportAntinociceptive effect induced by a combination of opioid and neurotensin moieties vs. their hybrid peptide [Ile9]PK20 in an acute pain treatment in rodents

- Activity of the drugs are related to the form of their administration.
- Compounds exerted spinal dose- and time-dependent analgesia.
- The mixture of both pharmacophores occurred to be more active than the chimera.
- Motor impairments surfaced as a side effect after application of the mixture.

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 [Ile9]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 [Ile9]PK20, motor impairments surfaced as a side effect. This in turn illustrates the advantageous use of hybrid structures over drug cocktails.