P-Affinity

Matejtschuk P. Affinity Separations A Practical Approach. New York Oxford University Press 1997. 

Opioid receptor binding Hydromorphone has a high affinity and selectivity for the p-opioid receptor, the p-affinity is about 10-fold higher than that of morphine. 

Opioid receptor affinity Tramadol (Frink et al., 1996) itself has a weak opioid receptor affinity, the active metabolite O-desmethyl-tramadol has p-selectivity and p-affinity about 10 times lower than that of morphine. 

Selected orally active compounds (Graudums et al. (Grunenthal GmbH), 1997 Sundermann et al. (Grunenthal GmbH), 2000) exhibited a wide range of p-opioid affinity (Ki 0.1 to 0.0001 pM) but affinities to the PAA and/or BTZ site were always quite constant (Ki 1 to 0.1 pM). Compounds with very pronounced p-affinities are at least 10 times more potent than morphine in vivo, have an excellent safety index and a relatively mild effect on respiration in comparison to other very strong opioids, e.g. fentanyl. 

Compounds with moderate p-affinities are very potent in a variety of pain models in mice and rats. In addition to antinociceptive efficacy in models of acute pain (tail flick, writhing) these compounds inhibit acute and persistent inflammatory pain (Randall Selitto, formalin test). Furthermore, they show strong inhibition of acute visceral pain (colorectal distension) and of tactile and cold allodynia in models of neuropathic pain (spinal nerve ligation (Chung), chronic constriction injury (Bennett)). The data suggest these compounds to be potential candidates for the management of clinical pain indications. Somatic and visceral pain with and without inflammatory conditions as well as neuropathic pain might be addressed with this approach. 

Mehta, P, Cummings, R D, McEver, R P, Affinity and kinetic analysis of P-selectin binding to P-selectin glycoprotein ligand-1, J. Biol Chem., 273, 32506-32513, 1998. 

Matejtschuk, P. Affinity Separations IRE Press at Oxford University Press Oxford, U.K., 1997. 

DeDonder, T, and Van Rysselberghe, P., Affinity. University Press, Stanford, California, 1936. 

Rappelons d autre part (Exp. i) que la donnee d un S-preschema P affine sur S k groups d operateurs G = Dg(M) revient k la donnee d une Algfebre quasi-coherente commutative graduee de type M sur S, i.e. d une Algfebre quasi-coherente A sur S, munie d une decomposition en somme directs (en tant que Module) ... 

Furthermore, the substitution of methyl groups at the T and 6 position of Tyr (Dmt) yielded Dmt-Tic- peptides (3) endowed with dramatically increased 8-affinity, comparable to the 8-affinity observed with deltorphins [59-63]. On the other hand, p-affinity of 3 rose 20-fold relative to 1 and 2, while k-affinity increased over 40-fold in guinea pig brain membranes, 20-fold in rat brain synaptosomes compared to 2 and approximately 40-fold for both membrane preparation relative to 1. Inclusion of the Tyr-D-Ala-Phe message domain (4) essentially eliminated opioid interaction with k-receptors, whereas 8- and p-affinities were only moderately altered in comparison to DYN (1-11) -NH2 (Table... 

Hsuan, J. Yaish, P. Affinity purification of active epidermal growth factor receptor using monoclonal antibodies. Methods Enzymol., 200, 378-388 (1991)... 

C Structural factor (depends on the pore structure of the adsorbent) P Affinity constant, m exponent, characteristic for adsorption system... 

Dubinin-Asthakov parmnetos fin N2 adsorption on samples at 77 K n, mrponoit characteristic energy La areragie micropore size P affinity coefficient. 

Parikh I, Cuatrecasas P. Affinity chromatography. Chem Eng News 1985 63 17-32. 

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