The behavioral responses exerted by spinal administration of the opioid-neurotensin hybrid peptide, PK23, were studied in adult male rats. The antinociceptive effect upon exposure to a thermal stimulus, as well as tol...The behavioral responses exerted by spinal administration of the opioid-neurotensin hybrid peptide, PK23, were studied in adult male rats. The antinociceptive effect upon exposure to a thermal stimulus, as well as tolerance development, was assessed in an acute pain model. The PK23 chimera at a dose of 10 nmol/rat produced a potent pain-relieving effect, especially after its intrathecal administration. Compared with intrathecal morphine, this novel compound was found to possess a favourable side effect profile characterized by a reduced scratch reflex, delayed development of analgesic tolerance or an absence of motor impairments when given in the same manner, though some animals died following barrel rotation as a result of its i.c.v. administration(in particular at doses higher than 10 nmol/rat). Nonetheless, these results suggest the potential use of hybrid compounds encompassing both opioid and neurotensin structural fragments in pain management. This highlights the enormous potential of synthetic neurotensin analogues as promising future analgesics.展开更多
According to wikipedia, hybrids are things combining the elements, and thus the properties of two different organisms. This definition is real also for chemical compounds as they can be made of two highly diverse and ...According to wikipedia, hybrids are things combining the elements, and thus the properties of two different organisms. This definition is real also for chemical compounds as they can be made of two highly diverse and independently acting moieties linked to each other. Such a unique construction gives the molecule new properties and activity pharmacologicaly greater than that observed for the sum of each pharmacophore alone. Furthermore, chimeras being multifunctional compounds exhibit an improved safety profile much in line with our requirements, compared to polytherapies composed of individual chimeric components.展开更多
基金financed by the EU—the European Regional Development Fund within the Operational Program“Innovative economy”for 2007-2013
文摘The behavioral responses exerted by spinal administration of the opioid-neurotensin hybrid peptide, PK23, were studied in adult male rats. The antinociceptive effect upon exposure to a thermal stimulus, as well as tolerance development, was assessed in an acute pain model. The PK23 chimera at a dose of 10 nmol/rat produced a potent pain-relieving effect, especially after its intrathecal administration. Compared with intrathecal morphine, this novel compound was found to possess a favourable side effect profile characterized by a reduced scratch reflex, delayed development of analgesic tolerance or an absence of motor impairments when given in the same manner, though some animals died following barrel rotation as a result of its i.c.v. administration(in particular at doses higher than 10 nmol/rat). Nonetheless, these results suggest the potential use of hybrid compounds encompassing both opioid and neurotensin structural fragments in pain management. This highlights the enormous potential of synthetic neurotensin analogues as promising future analgesics.
文摘According to wikipedia, hybrids are things combining the elements, and thus the properties of two different organisms. This definition is real also for chemical compounds as they can be made of two highly diverse and independently acting moieties linked to each other. Such a unique construction gives the molecule new properties and activity pharmacologicaly greater than that observed for the sum of each pharmacophore alone. Furthermore, chimeras being multifunctional compounds exhibit an improved safety profile much in line with our requirements, compared to polytherapies composed of individual chimeric components.
