Further investigations on the antinociceptive activity of tuftsin analogs.
C-Terminal dipeptide fragment of tuftsin, Pro-Arg, substituted by D-amino acids, and tuftsin analogs with n-hexyl- and n-heptylamine coupled to their C-termini were synthesized by a classical method in solution and their antinociceptive activity was measured by tail flick immersion test (0.4 microM/icv). D-Pro-D-Arg and D-Pro-L-Arg showed an analgesic activity, with the duration of 60 and 40 min, respectively. The strong behavioral effects observed after injection of D-Pro-D-Arg were decreased by naloxone. L-Pro-D-Arg and Thr-Lys-Pro-Arg-HxA display no antinociceptive effect; the tetrapeptide amide showed some toxicity effects. Thr-Lys-Pro-Arg-HpA was very toxic and caused death of all experimental animals. This effect was not influenced by previous injection of naloxone.
Nawrocka-Bolewska
E
E
Institute of Chemistry, Wrocław University, Poland.
Kubik
A
A
Szewczuk
Z
Z
Siemion
I Z
IZ
Obuchowicz
E
E
Gołba
K
K
Herman
Z S
ZS
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014405:Tuftsin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity
D000700:Analgesics; D004151:Dipeptides; D010446:Peptide Fragments; C074303:tuftsinyl-n-heptylamide; C074304:tuftsinyl-n-hexylamide; C045406:prolylarginine; D009270:Naloxone; D014405:Tuftsin