Highly potent neurotensin analog that causes hypothermia and antinociception.
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-neo5 degrees 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.
Tyler-McMahon
B M
BM
Laboratories of Neuropsychopharmacology, Mayo Foundation for Medical and Educational Research, Jacksonville, FL 32224, USA. tyler.beth@mayo.edu
Stewart
J A
JA
Farinas
F
F
McCormick
D J
DJ
Richelson
E
E
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007035:Hypothermia / Q000139:chemically induced*; D007274:Injections, Intraperitoneal; D008297:Male; D009496:Neurotensin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000700:Analgesics; D010446:Peptide Fragments; C407520:neurotensin (8-13), N-methyl-Arg(8)-Lys(9)-neo-Trp(11)-neo-Leu(12)-; D009496:Neurotensin; C054381:neurotensin (8-13)