Agents and actions. Supplements
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Agents Actions Suppl. · Jan 1993
ReviewSubstance P and inflammatory pain: potential of substance P antagonists as analgesics.
Substance P has been implicated in peripheral inflammatory responses and recent evidence from animal models indicates that substance P (NK-1 receptor) antagonists are effective in blocking peripheral inflammatory responses as well as nociception (pain) associated with inflammation. Evidence implicating substance P in nociception is reviewed in this survey, along with evidence on the effects of NK-1 receptor antagonists and with some comments on the usefulness of such antagonists as analgesics.
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Agents Actions Suppl. · Jan 1992
Studies on blood coagulation-fibrinolysis system regarding kallikrein-kinin system in the utero-placental circulation during normal pregnancy, labor and puerperium.
In our previous study (Adv. Exp. Med & Biol., 247B. 569. 1989, 198B. 41. 1986, blood & vessel, 17: 51. 1986), we reported on the mechanism of coagulation-fibrinolysis system and kallikrein-kinin system in the utero-placental circulation during normal pregnancy, labor and puerperium. ⋯ PAI. C and PIC incompletely inhibited the fibrinolytic activity of tPA by the active PAI. The kks shows a consumption of prekallikrein, LMW-kininogen and HMW-kininogen, and an overproduction of kinin in UV.
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Agents Actions Suppl. · Jan 1992
The bradykinin antagonist Hoe 140 inhibits carrageenan- and thermically induced paw oedema in rats.
The new and highly potent B2 bradykinin (BK) antagonist Hoe 140 was tested for its ability to inhibit oedema of rat paws induced by scalding and carrageenan. The data show that Hoe 140 inhibits scalding and carrageenan oedema for more than four and six hours, respectively. Based on its potency against actions of endogenously generated kinins Hoe 140 is appropriate to investigate the role of kinins in human inflammatory diseases.
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Agents Actions Suppl. · Jan 1992
Metabolism and characterisation of kinins and Hoe 140 (kinin antagonist) in the synovial fluid of patients with inflammatory joint diseases.
Methods have been optimised for the collection of synovial fluid and the chromatographic separation of individual kinins (bradykinin and kallidin) in the fluid by HPLC. In addition, the stability of the kinin antagonist, Hoe 140, in synovial fluid was compared with that of synthetic bradykinin. Although bradykinin was completely degraded after incubation for only 6 h in pooled synovial fluid obtained from patients with rheumatoid arthritis, Hoe 140 was stable for as long as 2 weeks under the same conditions. These studies will provide quantitative information regarding levels of kinins in inflamed joints and an insight into the therapeutic potential of kinin antagonists.
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Inflammatory pain is mediated from the periphery by a specialized subgroup of nerve fibers, the nociceptors. The nociceptive nerve endings undergo sensitization and excitation when stimulated with inflammatory agents. ⋯ Since nociceptive nerve endings are too small to be approached directly with the methods of intracellular electrophysiology, one has to extrapolate to the membrane channels and intracellular processes mediating nociceptor sensitization from studies on the perikarya of sensory ganglion cells. Sustained inflammation induces profound plastic changes in peripheral and central neurones leading to an altered excitability.