PubMed Health⌕ Search

Biomedical subjects

G Sarto

Publications and source records attributed to G Sarto.

At least 19 recordsLinked to original sources
PubMed1985

Synthesis and opioid activity of partial retro-inverso analogs of dermorphin.

We studied the effect of partial retro-inverso modification of selected peptide bonds of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2. The modifications concern two consecutive peptide bonds (Phe3-Cly4-Tyr5, I) or a single one (Gly4-Tyr5-, II or Phe3-Gly4, III). All pseudoheptapeptides showed low opioid activity in the in vitro and in vivo tests. Compound III has a biological potency comparable to that of morphine but only 2-5% of original dermorphin when tested in guinea pig ileum preparation and in mice tail-flick assay after intracerebro or subcutaneous administration.

Analgesia↗
PubMed1984

Structure-activity relationships for dermorphin-related tetrapeptides.

The opiate-like activity of six newly synthesized dermorphin-related tetrapeptides was determined in guinea pig ileum, mouse vas deferens and mouse tail-flick tests. Naloxone was a powerful antagonist of all compounds. Moreover, the biological activities of the compounds under examination were correlated in a statistically significant way to the lipophilic character of the C-terminal substituents and to an indicator variable taking into account the presence of an amidic group at the C-terminus.

Animals↗
PubMed1984

Synthesis and opioid activity of [Sar4]dermorphin-tetrapeptide analogues.

The modification of the dermorphin-(1-4)-tetrapeptide structure led to analogues with potent opioid activity in vitro and in vivo. [Sar4]Tetrapeptides such as H2N-CH(NH)-Tyr-D-Ala-Phe-Sar-D-NH-CH(CH3)C6H5 (VII) whose terminal amino group is replaced by the guanidino function and whose C-terminus is amidated by (R)-(+)-alpha-methylbenzylamine, show peripheral and central opioid activities comparable to or higher than those of dermorphin. The potency of VII in the different tests was as follows: guinea-pig ileum (GPI) IC50 = 0.09nM, mouse Vas deferens (MVD) IC50 = 0.69nM, tail-flick ED50 = 8.91 pmol/mouse, i.c.v. and 4.54 mumol/kg, s.c. This dermorphin-(1-4)-tetrapeptide derivative is about 650 and 950 times as active as morphine in the two in vitro tests, respectively. The MVD/GPI potency ratio of the new peptides suggests a mu-type agonist behaviour.

Animals↗
PubMed1983

Opioid peptides. Analgesic activity of potent dermorphin tetrapeptides. VI.

By employing the mouse tail-flick assay the analgesic activity of selected dermorphin tetrapeptides was assessed. The remarkable differences in potency exhibited by peptides after i.c.v. (500-1000 times higher than morphine) and s.c. (nearly comparable to morphine) administration are probably due to peptidase degradation.

Analgesics↗
PubMed1982

Opioid peptides. Structure-activity relationships in dermorphin tetrapeptides. I.

Characterisation and pharmacological data of twelve synthetic tetrapeptide analogs of dermorphin (opioid heptapeptide) are reported. An N-terminal tetrapeptide free acid or ester is less potent that the corresponding amide. Whereas substitution of Gly4 by another aminoacid residue is well tolerated, substitution of D-Ala2 by D- or L-alpha-aminoxypropionic acid causes a complete loss of activity. Finally, guanidination of the tetrapeptides results in an increase of peripheral and central opioid activity.

Animals↗
PubMed1982

Opioid peptide. Structure-activity relationships in dermorphin tetrapeptide-amides. II.

Preliminary pharmacological data and the characterization of sixteen synthetic tetrapeptide-amide analogs of dermorphin (opioid heptapeptide) are reported. N,N-dialkylamides displayed reduced or no activity; on the contrary, derivatization of H-Tyr-D-Ala-Phe-Gly-OH C-terminus by suitable amide moieties (1-adamantanamine, 1-adamantane-methylamino, or D-alpha-methylbenzylamine) produced potent analogues with peripheral and central opioid activities comparable to, or higher than those of dermorphins.

Analgesics↗
PubMed1981

[Modulation of the effect of morphine on the isolated guinea pig intestine by noradrenaline and serotonin].

The interference of NA and 5-HT on Morphine inhibition on electrically-driven guinea-pig ileum was investigated. The alpha-antagonist Phentolamine (1 gamma/ml) and alpha MT-pretreatment reduced Morphine inhibition on muscle twitch. Similarly, ilea taken from pCPA-pretreated animals were less sensitive to the opioid. In contrast, both NA or 5-HT added either to normal or to amine-depleted tissue enhance Morphine inhibition. Therefore, not only in the brain but also in the guinea-pig ileum NA and 5-HT enhanced opioid effect.

Animals↗