A highly selective NK-2 tachykinin receptor antagonist containing D-tryptophan.
The classical approach used in the development of substance P (SP) antagonists, i.e. the introduction of multiple D-tryptophan (D-Trp), was successfully extended to neurokinin A (NKA). Thus, a new NK-2-selective tachykinin receptor antagonist, namely [Tyr5, D-Trp6,8,9, Arg10]NKA-(4-10), was developed that had pA2 values of 5.2, 7.9 and 4.9 in three monoreceptor in vitro assays for NK-1, NK-2 and NK-3 tachykinin receptors, respectively.
Rovero
P
P
Peptide Synthesis Laboratory, Chemistry Department, A. Menarini Pharmaceuticals, Firenze, Italy.
Pestellini
V
V
Maggi
C A
CA
Patacchini
R
R
Regoli
D
D
Giachetti
A
A
D000595:Amino Acid Sequence; D000818:Animals; D004285:Dogs; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D014364:Tryptophan / Q000032:analysis*
D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; C063615:neurokinin A (4-10), Tyr(5)-Trp(6,8,9)-Arg(10)-; D015288:Neurokinin A; D014364:Tryptophan; C056408:neurokinin A(4-10)