Substance P: structure, function, and therapeutics.
Extensive efforts since 1931, on the structural determination of the mammalian tachykinin SP by NMR, CD and IR have turned out to be inconclusive. Studies are now being concentrated on the structural properties and characteristics of various NK receptors (NK(1), NK(2) and NK(3)) with the help of genetics, cloning, receptor engineering, mutagenesis and modeling. This knowledge is now being fruitfully used in the development of non-peptide NK(1) receptor antagonists that essentially block the pharmacological effects of SP. It is now being realized that the simultaneous blockade of two or more receptors gives promising results in emesis, depression and pulmonary obstructive diseases. In addition to the synthetic compounds, the discovery of antagonists from natural origin has added a great value to this field. In this review we have made an attempt to present the structural characteristics of SP, its analogs and antagonists, the structural characteristics of the NK receptor, and structure activity relationships that have helped to improve the therapeutic utilities of SP antagonists.
Datar
Prasanna
P
Department of Chemistry, Bombay College of Pharmacy, Kalina, Mumbai, India.
Srivastava
Sudha
S
Coutinho
Evans
E
Govil
Girjesh
G
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017433:Protein Structure, Secondary; D018040:Receptors, Neurokinin-1 / Q000737:chemistry / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use
D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D013373:Substance P