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The manufacture of pharmaceutical products made under good manufacturing practices (GMP) must comply with the guidelines of national regulatory bodies based on international or regional compendia. The existence of this type of regulation allows pharmaceutical laboratories to count on the standardization of high-quality production processes, obtaining a safe product for human use, with a positive impact on public health. In addition, the COVID-19 pandemic highlights the importance of having more and better-distributed manufacturing plants, emphasizing regions such as Latin America. This review shows the most important GMP standards in the world and, in particular, their relevance in the production of vaccines and antibodies., Competing Interests: Author TD was employed by the company Deeks Pharmaceutical Consulting Services. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Covarrubias, Rivera, Soto, Deeks and Kalergis.)

Three analogues of leucine enkephalin, in which the terminal tyrosine-1 residue has been replaced by conformationally restrained aromatic amino acids, have been synthesized by classical solution methods. Their opiate agonist potencies on electrically stimulated guinea pig ileum and mouse vas deferens preparations were determined and compared with morphine, Met enkephalin, and Leu enkephalin. None of these analogues had analgesic properties when evaluated on the above tissue preparations or when evaluated by the hot-plate test in mice after subcutaneous and intracerebroventricular administration.

Two analogues of Leu-enkephalin, in which the terminal tyrosine-1 residue has been replaced by a conformationally restrained tyrosine analogue, have been synthesized by classical solution methods, and their opiate agonist potencies on electrically stimulated guinea pig ileum and mouse vas deferens preparations were determined in comparison with Leu-enkephalin. The restriction in the degree of freedom of the tyrosine moiety in [(2-amino-6-hydroxy-2-tetralinyl)carbonyl]glycylglycylphenylalanylleucine methyl ester (3e) leads to a 7 to 8 times higher agonist activity at the mu-receptor subtype in guinea pig ileum when compared to Leu-enkephalin, and an almost 30-fold decrease in potency, vs. Leu-enkephalin, on mouse vas deferens preparation. [(2-Amino-5-hydroxy-2-indanyl)carbonyl]-glycylglycylphenylalanylleucine methyl ester (2e) was inactive in the above tests. These results demonstrate the differential effect of restricting conformational flexibility on receptor recognition. Neither analogue had any analgesic properties when evaluated by the hot-plate test in mice after sc and icv administration.