[Analgesic activity of dermorphin and its proline analogs].
Dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2; DM) and its analogs obtained via stereochemical transformation of L-Pro6 to D-Pro6 peptide in DM ([Dpro6]DM) and via dehydration of L-Pro6 peptide ([dHPro6]DM) were characterized with respect to the analgesic activity in rats tested under conditions corresponding to various levels of pain sensitivity organization. The drugs were introduced by intraperitoneal injections in various doses (0.1, 1.0, and 10 mg/kg). In the case of acetic-acid induced convulsions (writhing), DM and [Dpro6]DM produced analgesic action in the minimum dose, while the analogous effect of [dHPro6]DM was observed only in greater doses. In the tail-clamp (Haffner) test, DM and [Dpro6]DM also inhibited nociception while the latter compound was ineffective. In the grid-shock test, [Dpro6]DM showed a higher activity than [dHPro6]DM, whereas DM did not produce analgesic action. Thus, all the studied peptides exhibit pronounced analgesic activity, and the replacement of L-Pro6 in DM by its stereomer D-Pro is more effective than the substitution of dHPro6.
Guzevatykh
L S
LS
Valuĭskiĭ
D V
DV
Voronina
T A
TA
Emel'ianova
T G
TG
Andreeva
L A
LA
Alfeeva
L Iu
LIu
Seredenin
S B
SB
Miasoedov
N F
NF
D019943:Amino Acid Substitution; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000737:chemistry*; D000818:Animals; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry*; D018847:Opioid Peptides; D010146:Pain / Q000188:drug therapy; D017288:Pain Threshold / Q000187:drug effects*; D011392:Proline / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin; D011392:Proline