Adjuvant activity of some nonpyrogenic hydrophobic analogues of muramyl dipeptide in enhancing the primary humoral and cell mediated immune responses in guinea pig model.

Five muramyl dipeptide analogues synthesized by derivatization of gamma-carboxyl of D-isoglutamine residue of MDP into alkyl amides or incorporation of lysine residue at the site via epsilon-NH2 function were evaluated for immuno-adjuvant activity. Derivatization of gamma-carboxyl of D-isoglutamine into butyl, octyl and dibutyl residues stimulated delayed type of hypersensitivity (DTH) response, the maximum stimulation being observed with octyl amide. Introduction of lauryl amide residue abolished DTH response. The antibody response was impaired with all the alkyl amide analogues except for the lysyl amide derivative with which the response was higher than MDP. Correlation was observed between DTH response and macrophage migration.

Morphine-like activity of some N-substituted amides of met-enkephalin.

Opioid activity of a homologous series of met-enkephalin alkylamides was analysed. In guinea pig ileum test, the hexylamide derivative was most active, whereas the isopropylamide derivative was most potent in analgesia test. The results suggest that structural changes of this type at the C-terminus of the pentapeptide improve the opioid activity.

Morphine-like activity of substituted amides & imides of [D-Ala2, Met5]-enkephalin.

Six enkephalin analogues (N-substituted amides and imides of [D-Ala2, Met5]-enkephalin) were synthesized and tested for opioid activity. All the compounds, except one i.e., compound IV, showed analgesic activity which was much higher than Met-enkephalin and morphine in mice and inhibited electrically induced contractions of isolated guineapig ileum, [D-Ala2, Met5]-enkephalin-morpholide and [D-Ala2, Met5]-enkephalin-beta-Ala-amide were the most potent analgesics and nearly 6 and 500 times as active as morphine and Met-enkephalin respectively. Both the compounds were equipotent on the guineapig ileum preparation, whereas the beta-Ala-amide was about twice as active as the morpholide in the electrically stimulated mouse vas deferens preparation.