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      Substance P: a pioneer amongst neuropeptides

      , ,
      Journal of Internal Medicine
      Wiley

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          Most cited references74

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          An unidentified depressor substance in certain tissue extracts.

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            Distinct mechanism for antidepressant activity by blockade of central substance P receptors.

            The localization of substance P in brain regions that coordinate stress responses and receive convergent monoaminergic innervation suggested that substance P antagonists might have psychotherapeutic properties. Like clinically used antidepressant and anxiolytic drugs, substance P antagonists suppressed isolation-induced vocalizations in guinea pigs. In a placebo-controlled trial in patients with moderate to severe major depression, robust antidepressant effects of the substance P antagonist MK-869 were consistently observed. In preclinical studies, substance P antagonists did not interact with monoamine systems in the manner seen with established antidepressant drugs. These findings suggest that substance P may play an important role in psychiatric disorders.
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              Altered nociception, analgesia and aggression in mice lacking the receptor for substance P.

              The peptide neurotransmitter substance P modulates sensitivity to pain by activating the neurokinin-1 (NK-1) receptor, which is expressed by discrete populations of neurons throughout the central nervous system. Substance P is synthesized by small-diameter sensory 'pain' fibres, and release of the peptide into the dorsal horn of the spinal cord following intense peripheral stimulation promotes central hyperexcitability and increased sensitivity to pain. However, despite the availability of specific NK-1 antagonists, the function of substance P in the perception of pain remains unclear. Here we investigate the effect of disrupting the gene encoding the NK-1 receptor in mice. We found that the mutant mice were healthy and fertile, but the characteristic amplification ('wind up') and intensity coding of nociceptive reflexes was absent. Although substance P did not mediate the signalling of acute pain or hyperalgesia, it was essential for the full development of stress-induced analgesia and for an aggressive response to territorial challenge, demonstrating that the peptide plays an unexpected role in the adaptive response to stress.
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                Author and article information

                Journal
                Journal of Internal Medicine
                J Intern Med
                Wiley
                0954-6820
                1365-2796
                January 2001
                January 2001
                : 249
                : 1
                : 27-40
                Article
                10.1046/j.0954-6820.2000.00773.x
                81150b53-8bc2-4eb5-bffe-8d1fb9902581
                © 2001

                http://doi.wiley.com/10.1002/tdm_license_1.1

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