TY - JOUR
T1 - Highly potent neurotensin analog that causes hypothermia and antinociception
AU - Tyler-Mcmahon, Beth M.
AU - Stewart, Jennifer A.
AU - Farinas, Fernando
AU - McCormick, Daniel J.
AU - Richelson, Elliott
N1 - Funding Information:
This work was supported by the Mayo Foundation and grants from the N.I.M.H. (ER) and N.I.N.D.S. (BMT).
PY - 2000/2/25
Y1 - 2000/2/25
N2 - The tridecapeptide neurotensin has long been proposed as an endogenous neuroleptic. However, for neurotensin [or neurotensin(8-13) [NT(8-13)], the active fragment] to cause its effects, it must be administered centrally. Here, we report on an analog of NT(8-13), (N-methyl-Arg),Lys,Pro,L-neo-Trp,tert-Leu,Leu (NT69L), which contains a novel amino acid, L-neo-tryptophan and exhibits high affinity for the rat and human neurotensin receptor, subtype 1. After intraperitoneal (i.p.) injection (1 mg/kg), NT69L induced hypothermia of >5°C (rectal), with a significant effect persisting for over 7 h. NT69L also caused a rapid (within 15 min) and persistent (for over 5 h) antinociceptive effect, as determined by the hot plate test. NT69L was overall the most potent and longest lasting neurotensin analog that has been reported. These studies provide the background for further testing of a stable, potent and long lasting neurotensin analog as a potential neuroleptic. Copyright (C) 2000 Elsevier Science B.V.
AB - The tridecapeptide neurotensin has long been proposed as an endogenous neuroleptic. However, for neurotensin [or neurotensin(8-13) [NT(8-13)], the active fragment] to cause its effects, it must be administered centrally. Here, we report on an analog of NT(8-13), (N-methyl-Arg),Lys,Pro,L-neo-Trp,tert-Leu,Leu (NT69L), which contains a novel amino acid, L-neo-tryptophan and exhibits high affinity for the rat and human neurotensin receptor, subtype 1. After intraperitoneal (i.p.) injection (1 mg/kg), NT69L induced hypothermia of >5°C (rectal), with a significant effect persisting for over 7 h. NT69L also caused a rapid (within 15 min) and persistent (for over 5 h) antinociceptive effect, as determined by the hot plate test. NT69L was overall the most potent and longest lasting neurotensin analog that has been reported. These studies provide the background for further testing of a stable, potent and long lasting neurotensin analog as a potential neuroleptic. Copyright (C) 2000 Elsevier Science B.V.
KW - Hot plate test
KW - NT(8-13)
KW - NT69L
UR - http://www.scopus.com/inward/record.url?scp=0034712010&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034712010&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(99)00877-8
DO - 10.1016/S0014-2999(99)00877-8
M3 - Article
C2 - 10708713
AN - SCOPUS:0034712010
SN - 0014-2999
VL - 390
SP - 107
EP - 111
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-2
ER -