Treatment of relapses

Gairín, Xavier Montalbán; Nos, Carlos

doi:10.4324/9780203212974_chapter_26

Cited by 2 publications

(2 citation statements)

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“…One of the most potent and selective peptide opioid receptor agonists reported appears to be [~-Pro'O]Dyn A1-11-OH (DPDYN), which was reported to have a ti vs. p selectivity of 62 and a high binding affinity of 0.032 nM against the K ligand [3H]bremazocine. In tissue bioassays DPDYN displays a hamster was deferens (HVD) (6) vs. guinea pig ileum (GPI) ( p and ti) Ic50 ratio of 280, with an ICso = 3.3 nM in the GPI (18). On the other hand, we have recently shown (1 9) that the cyclic dynorphin analogue [ PAn5, C;s"]Dyn Al-11-NH2 is highly K selective vs. the 6 receptor, with a ti vs. 6 selectivity of 165 and a binding affinity at the K receptor 0.52 nM.…”

Section: H-tyr-gly-gly-phe-leu-arg-arg-ile-arg-pro-lys-mentioning

confidence: 99%

Syntheses, opioid binding affinities, and potencies of dynorphin A analogues substituted in positions 1, 6, 7, 8 and 10

Kawasaki

Knapp

Walton

et al. 1993

International Journal of Peptide and Protein Research

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Structural, stereochemical, stereoelectronic and conformational requirements for biological activity of dynorphin A1–11‐NH2 analogues at opioid receptors were explored by substitution of Tyr1, Arg6, Arg7, Ile8 and Pro10 with other amino acid residues. Interestingly, substitution of Tyr1 with Nα‐Ac‐Tyrl, D‐Tyr1, Phe1 or p‐BrPhe1 led to analogues that were quite potent at κ opioid receptors, and additional substitution of Ile8with D‐Ala8 and/or Pro10 with D‐Pro10 retained high potency in brain binding assay: [Nα‐Ac‐Tyr1]‐ (1), [D‐Tyr1]‐ (2) [Phe1]‐ (3), [Phe1. D‐Ala8]‐ (5), [p‐BrPhe1, D‐Alas]‐ (6), [Phe1, D‐Pro10]‐ (7) and [Phe1, D‐Ala8, D‐Pro10]‐Dyn A1–11‐NH2 (8) had IC50(nM) binding affinities of 13.2, 18.6, 1.64, 1.26, 1.84, 2.44 and 1.62 nM, respectively. The D‐Phe1 analogue 4, however, was only weakly active (610 nM). All of the analogues except 4 were modestly selective for κ vs. μ guinea pig brain opioid receptor (11‐ to 88–fold) and quite selective for κ vs. δ receptors (65–576). However, all of the analogues appeared to have very low or essentially no activity in the guinea pig ileum and mouse vas deference functional bioassays, and one analogue, 5, appeared to have weak antagonist activities. On the other hand, if constrained amino acids such as β‐methylphenylalanine or 1,2,3,4‐tetrahydroisoquinoline carboxylic acid, and hydroxyproline were placed in the 1 position, inactive analogues or analogues with greatly reduced potency and biological activity were obtained (compounds 12–14). It had previously been suggested that the Arg6 and Arg7 residues were critical for biological activity. However, when we replace either one of these residues, [Nle6]Dyn A1–11 (9) and [Nle7]Dyn A1–11‐NH2 (10) were both highly potent binders in κ receptor binding studies (IC50= 0.95 and 0.43 nM, respectively), and interestingly also were potent in μ and δ binding studies. Furthermore, both of the analogues were modestly potent in the GPI and MVD assays (94, 65 nM; 31, 81 nM, respectively). These results demonstrate that basic residues at positions 6 and 7 in dynorphin are not very important for binding to κ opioid receptors. Finally, many of the compounds reported here showed high selectivity for central vs. peripheral κ opioid receptors, with compound 4 being the most selective (63 000‐fold).

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Section: H-tyr-gly-gly-phe-leu-arg-arg-ile-arg-pro-lys-mentioning

confidence: 99%

Syntheses, opioid binding affinities, and potencies of dynorphin A analogues substituted in positions 1, 6, 7, 8 and 10

Kawasaki

Knapp

Walton

et al. 1993

International Journal of Peptide and Protein Research

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“…En este trabajo, el test se conformó por 22 ítems, distribuidos en cuatro componentes: afectivo, comportamental, cognoscitivo y amplificación. Contó con tres alternativas de respuesta: de acuerdo, sin opinión, en desacuerdo; el cual fue adaptado por Martínez (2006) de la escala original de Gairín (1987). La muestra estuvo conformada por 437 estudiantes, a los que se les realizó un análisis de un antes y un después del proceso de aprendizaje, evidenciando una mejorando de manera satisfactoria en el rendimiento de los estudiantes, por lo que resaltaron la importancia de elaborar materiales específicos que se ajusten a los contenidos básicos y a las características de los estudiantes, siguiendo directrices adaptativas.…”

Section: Aprendizaje Adaptativo: Estrategia Para Los Modelos De Intel...unclassified

Estrategias de aprendizaje adaptativo en Ciencias de la Educación y Sociales: Test adaptativos informatizados

2020

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Treatment of relapses

Cited by 2 publications

References 1 publication

Syntheses, opioid binding affinities, and potencies of dynorphin A analogues substituted in positions 1, 6, 7, 8 and 10

Syntheses, opioid binding affinities, and potencies of dynorphin A analogues substituted in positions 1, 6, 7, 8 and 10

Estrategias de aprendizaje adaptativo en Ciencias de la Educación y Sociales: Test adaptativos informatizados

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