Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.11 (
CD10
)
9,792
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A growing body of evidence suggests that peptides may possess analgesic effects without tolerance development. The synthetic tetrapeptide Tyr-d-Arg-Phe-Gly-NH
2
was modified with the inclusion of a (d-Arg)
8
vector to prevent the action of
endopeptidase
and to increase the duration of the analgesic action of the tetrapeptide when administered orally. The aim of this study was to estimate the analgesic efficacy of the tetrapeptide with (d-Arg)
8
(tridecapeptide,
TDP
) in experimental models of acute and chronic pain. The analgesic effects of
TDP
were estimated using a model of acute visceral pain in mice (writhing test) and a model of chronic neuropathic pain (chronic constriction injury (CCI) of the sciatic nerve) in rats. The intravenous administration of morphine (0.32-1mg/kg) and
TDP
(0.32-1.8mg/kg) produced significant dose-related antinociceptive effects in the writhing test. The potency of
TDP
after i.g. administration was lower than that after i.v. administration but comparable with that of i.g. morphine. In the CCI model,
TDP
(0.1, 1 and 10mg/kg, i.g.) induced marked analgesia with repeated administration without any signs of tolerance. The single administration of
TDP
after morphine treatment (7days) produced a significant analgesic effect in morphine-tolerant rats, indicating the absence of cross-tolerance between these two drugs. The combined administration of
TDP
and morphine resulted in the reduction of analgesic tolerance to morphine. The absence of cross-tolerance to morphine and the ability to prevent morphine tolerance allows this compound to be a prospective candidate for chronic pain therapy. In order to find the target receptors for
TDP
, a docking study was performed. It was found that the molecule can bind to the NMDA receptor using electrostatic, hydrogen bonding and hydrophobic interactions.
...
PMID:A new tridecapeptide with an octaarginine vector has analgesic therapeutic potential and prevents morphine-induced tolerance. 2917 19
