Dariusz Kosson

Polish Academy of Sciences, Warszawa, Masovian Voivodeship, Poland

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Publications (7)14.79 Total impact

  • No preview · Article · Sep 2010 · Pharmacological reports: PR
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    ABSTRACT: Biphalin is an opioid peptide analogue that currently is under clinical development as a new type of site-directed analgesic. In rats, the intrathecal (i.t.) analgesic potency of biphalin is 1000-fold greater than morphine. Such a high activity may reflect this compound's activation of three types of opioid receptors (mu, delta and kappa). NMDA receptors also play an important role in nociceptive processing. Therefore, we investigated in rats whether an NMDA antagonist may influence biphalin-induced antinociception. In the present study, ketamine was chosen because of the widespread safe use of this drug in clinical practice. I.t. application of ketamine alone had relatively little analgesic effect and its excitatory effects limited possible doses of the drug. Co-administration of ketamine with biphalin or morphine produced markedly greater antinociception than biphalin or morphine alone in acute, thermal tail flick testing. These results suggest that NMDA antagonists may be useful potentiators of biphalin analgesia. Thus, to obtain the same spinal antinociceptive effect, lower doses of biphalin or morphine are required when ketamine is co-administered.
    No preview · Article · Aug 2008 · European journal of pain (London, England)
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    ABSTRACT: The opioid peptide dimmer biphalin [(Tyr-D-Ala-Gly-Phe-NH-)(2)] has high potency both in vivo and in vitro. Its antinociceptive activity depends on the route of administration: the lowest potency is after subcutaneous, and the highest after intrathecal or inracerebroventricular administration. We tested the analgesic activity of biphalin in a wide range of doses after intrathecal administration to rats. Doses as low as 0.005 nmol produced significant analgesia. Increasing the dose up to 2 nmol elevated and prolonged antinociception without any evident side effects, indicating that biphalin is an extremely potent opioid after intrathecal application with a wide therapeutic window. The highest dose tested (20 nmol) produced full analgesia and body rigidity lasting 2-3 h. After muscle tone returned to normal, antinociception lasted for several more hours. During these studies we observed a correlation between responses to biphalin and catheter placement. Postmortem verification of catheter placement revealed that in those rats in which high-dose biphalin did not produce analgesia or muscle rigidity, the catheter was positioned incorrectly or the flow of drug solution was obstructed. Therefore, a secondary conclusion is that assessment of transient rigidity after administration of a high dose of biphalin may be used as an easy method to confirm intrathecal placement of the catheter.
    Full-text · Article · Jul 2005 · Pharmacological reports: PR
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    ABSTRACT: The discovery of numerous endogenous neuropeptides that participate in the formation, transmission, modulation, and perception of pain signals offers numerous strategies for the development of new analgesics. Nevertheless, the same research has not yet replaced opioids as the gold standard of pain treatment. Therefore, one possible avenue of drug development may shift interest from searching for receptor-selective opioids to creating an arsenal of drugs that target multiple opioid and non-opioid sites simultaneously. The presented short review focuses on the development of potential analgesic peptidomimetic compounds based upon opioid neuropeptides and substance P.
    Full-text · Article · Jan 2004 · Pure and Applied Chemistry
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    ABSTRACT: Previous studies of structure-activity of biphalin defined fragments which expressed the full biological potency of the parent compound. The most simple fragment was Tyr-D-Ala-Gly-Phe-NH-NH<--X, where X=Phe, but it also could be other hydrophobic amino acids. This paper presents data that replacement of the phenylalanine with a dansyl (X=DNS) groups gives an analogue (AA2016) that fully preserves the high affinity of the initial analogue for both mu and delta opioid receptors. In the tail flick test in rats, intrathecal injection of the compound produces strong antinociception, comparable to the parent biphalin. Because AA2016 contains a strong fluorescent group, it can be a very useful tool for prospective studies in vivo, including biological barrier permeability, tissue distribution, metabolism and receptor-ligand complex formation.
    No preview · Article · Jan 2002 · Life Sciences

  • No preview · Article · Oct 2000 · Transplantation Proceedings
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    ABSTRACT: It is possible that peripheral analgesic targets may enhance central analgesia. We present our preliminary results of selected opioid peptides on morphine (MOR) analgesia. Coinjection of dermorphin with MOR resulted in antinociceptive synergy, whereas morphiceptin coinjected with MOR yielded antinociceptive activity lower than MOR alone. At lower doses of MOR, DADLE strongly potentiates analgesia, but at higher doses of MOR, DADLE inhibits the antinociceptive effect of MOR.
    No preview · Article · Feb 1994 · Regulatory Peptides