Summary
The involvement of tachykinin neuropeptides, such as substance P and the neurokinins, in pain transmission is supported by a wealth of evidence. At present. the therapeutic potential of manipulating tachykinin-mediated effects is being investigated and has been assisted by the discovery of several non-peptide, metabolically stable compounds that are antagonists at neurokinin (NK) receptors. Since multiple neurotransmitters or neuromodulators are involved in nociception in primary afferents, drugs that are antagonists at both tachykinin NK1 and NK2receptors could be clinically more useful than receptor-selective drugs in the treatment of pain syndromes. NK1 receptor antagonists that are also opioid receptor agonists or the combination of neurokinin receptor antagonists with opioids may also be promising approaches to treating pain.
Similar content being viewed by others
References
Erspamer V. The tachykinin peptide family. Trends Neurosci 1981; 4: 267–9
Pernow B. Substance P. Pharmacol Rev 1983; 35: 85–141
Maggio JE. Tachykinins. Annu Rev Neurosci 1988; 11: 13–28
Maggi CA, Patacchini R, Rovero P, et al. Tachykinin receptors and tachykinin receptor antagonists. J Auton Pharmacol 1993; 13: 23–93
Kangawa K, Minamino N, Fukuda A et al. Neuromedin K: a novel mammalian tachykinin identified in porcine spinal cord. Biochem Biophys Res Commun 1983; 114: 533–40
Kimura S, Okada M. Sugita Y, et al. Novel neuropeptides, neurokinin α and β isolated from porcine spinal cord. Proc Jpn Acad 1983; 59B: 101–4
Nawa H, Hirose T, Takashima H et al. Nucleotide sequences of clonal cDNAs for two types of bovine brain substance P precursor. Nature 1983; 306: 32–6
McDonald MR, Takeda J, Rice CM, et al. Multiple tachykinins are produced and secreted upon posttranslalional processing of the three substance P precursor proteins, α, β. and γ-preprotachykinin. J Biol Chem 1989; 264: 15578–92
Buck SH, Burcher E. The tachykinins: a family of peptides with a brood of ‘receptor’. Trends Pharmacol Sci 1986; 7: 65–8
Regoli D, Drapeau G, Dion S, et al. Pharmacological receptors for substance P and neurokinins. Life Sci 1987; 40: 109–17
Quirion R, Dam T-V. Multiple neurokinin receptors: recent developments. Regul Pept 1988; 22: 18–25
Guard S, Watson SP. Tachykinin receptor types: classification and membrane signalling mechanisms. Neurochem Int 1991; 18: 149–65
Nakanishi S. Mammalian tachykinin receptors. Annu Rev Neurosei 1991; 14: 123–36
Masu Y, Nakayama K, Tamaki H, et al. cDNA cloning of bovine substance-K receptor through oocyte expression system. Nature 1987; 329: 836–8
Yokota Y, Sasai Y, Tanaka K, et al. Molecular characterization of a functional cDNA for rat substance P receptor. J Biol Chem 1989; 264: 17649–52
Hershey AD, Krause JE. Molecular characterization of a functional cDNA encoding the rat substance P receptor. Science 1990; 247: 958–62
Shigemoto R, Yokota Y, Tsuchida K, et al. Cloning and expression of a rat neuromedin K receptor cDNA. J Biol Chem 1990; 265: 623–8
Otsuka M, Yoshioka K. Neurotransmitter functions of mammalian tachykinins. Physiol Rev 1993; 73: 229–308
Buck SH, editor. The tachykinin receptors. Totowa (NJ): Humana Press, 1994
Regoli D, Boudon A, Fauchcrc J-L. Receptors and antagonists for substance P and related peptides. Pharmacol Rev 1994; 46: 551–99
Lonemore J, Swain CJ, Hill RG. Neurokinin receptors. Drug News Perspect 1995; 8: 5–23
Pataechini R, Maggi CA. Tachykinin receptors and receptor subtypes. Arch Int Pharmacodyn Ther 1995; 329: 161–84
McLean S. Neuropeptide antagonists of the NK1 tachykinin receptor. Med Res Rev 1996; 16: 297–317
Fields HL, Heinricher MM, Mason P. Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci 1991; 14: 219–45
Hokfelt T, Johansson O, Ljundahl A, et al. Peptidergic neurones. Nature 1980; 284: 515–21
Nicoll RA, Schenker C, Leeman SE. Substance P as a transmitter candidate. Annu Rev Neurosei 1980; 3: 227–68
Henry JL. Relation of substance P to pain transmission: neurophysiological evidence. In: Porter R, O’Connor M, editors. Substance P in the nervous system. Ciba Foundation Symposium 91. London: Pitman. 1982: 206–17
Hökfelt T, Kellerth J-O, Nilsson G, et al. Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons. Brain Res 1975; 100: 235–52
Hökfelt T, Kellerth J-O, Nilsson G, et al. Substance P: localization in the central nervous system and in some primary sensory neurons. Science 1975; 190: 889–91
Cuello AC, Jessell TM, Kanazawa I, et al. Substance P-localization in synaptic vesicles in rat central nervous system. J Neurochem 1977; 29: 747–51
Light AR, Perl ER. Spinal termination of functionally identified primary afferent neurons with slowly conducting myelinated fibers. J Comp Neurol 1979; 186: 133–50
Sugiura Y, Lee CL, Perl ER. Central projections of identified, unmyelinated (C) afferent fibers innervating mammalian skin. Science 1986; 234: 358–61
Lynn B. Perl ER. Afferent mechanisms of pain. In: Kruger L. editor. Handbook of perception and cognition. 2nd ed. Pain and touch. San Diego: Academic Press, 1996: 213–41
Yaksh TL, Jessell TM, Gamse R, et al. Intrathecal morphine inhibits substance P release from mammalian spinal cord in vivo. Nature 1980; 286: 155–7
Duggan AW, Hendry IA. Laminar localization of the sites of release of immunoreactive substance P in the dorsal horn with antibody coated microelectrodes. Neurosci Lett 1986; 68: 134–40
Brodin E, Linderoth B, Gazelius B, et al. In vivo release of substance P in cat dorsal horn studied with microdialysis. Neurosei Lett 1987; 76: 357–62
Duggan AW, Hendry AL Morton CR, et al. Cutaneous stimuli releasing immunoreactive substance P in the dorsal horn of the cat. Brain Res 1988; 451: 261–73
Holzer P. Capsaicin: cellular targets. mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev 1991; 43: 143–201
Holzer P. Peptidergic sensory neurons: neuropharmacological and pathophysiological implications. In: Asbury AK, Budka H. Sluga E, editors. Sensory neuropathies. Vienna: Springer-Verlag, 1995: 13–24
Maggi CA. Tachykinin and calcitonin gene-related peptide (CGRP) as co-transmitters released from peripheral endings of sensory nerves. Prog Neurobiol 1995; 45: 1–98
Cuello AC, Jessell TM, Kanazawa I, et al. Substance P-localization in synaptic vesicles in rat central nervous system. J Neurochem 1977; 29: 747–51
Takahashi T, Otsuka M. Regional distribution of substance P in the spinal cord and nerve roots of the cat and the effect of dorsal root section. Brain Res 1975; 87: 1–11
Yashpal K, Dam T-V, Quirion R. Quantitative autoradiographic distribution of multiple neurokinin binding sites in rat spinal cord. Brain Res 1990; 506: 259–66
Sakurada T, Yamada T, Sakurada S, et al. Substance P analogues containing D-histidine antagonize substance P-induced behavioural effects at the spinal level in mice. Eur J Pharmacol 1989; 174: 153–60
Sakurada T, Kuwahara H, Sakurada S, et al. Behavioural assessment as substance P antagonists in mice. Neuropeptides 1987; 9: 197–206
Yashpal K, Wright DM, Henry JL. Substance Preduces tail-flick latency: implication for chronic pain syndrome. Pain 1982; 14: 155–67
Matsumura H, Sakurada T, Hara A, et al. Characterization of the hyperalgesic effect induced by intrathecal injection of substance P. Neuropharmacology 1985; 24: 421–6
Battaglia G, Rustioni A. Coexistence of glutamate and substance Pin dorsal root ganglion neurons of the rat and monkey. J Comp Neurol 1988; 277: 302–12
De Biasi S, Rustioni A. Glutamate and substance P coexist in primary afferent terminals in the superficial laminae of spinal cord. Proc Natl Acad Sci USA 1988; 85: 7820–4
Randic M, Hecimovie H, Ryu PD. Substance P modulates glutamate induced currents in acutely isolated rat spinal dorsal horn neurones. Neurosci Lett 1990; 117: 74–80
Mjellem-Joly N, Lund A, Berge O-G, et al. Potentiation of a behavioural response in mice by spinal coadministration of substance P and excitatory amino acid agonists. Neurosci Lett 1991; 133: 121–4
Duggan AW. Release of neuropeptides in the spinal cord. Prog Brain Res 1995; 104: 198–223
Juranek I, Lembeck F. Evidence for the participation of glutamate in reflexes involving afferent, substance P-containing nerve fibres in the rat. Br J Pharmacol 1996; 117: 71–8
Mendell LM. Physiological properties of unmyelinated fibre projections to the spinal cord. Exp Neurol 1966; 16: 316–32
Dalsgaard C-J, Haegerstrand A, Theodorsson-Norheim E, et al. Neurokinin A-like immunoreactivity in rat primary sensory neurons: coexistence with substance P. Histochemistry 1985; 83: 37–40
Ogawa T, Kanazawa I, Kimura S. Regional distribution of substance P. neurokinin A and neurokinin B in rat spinal cord, nerve roots and dorsal root ganglia and the effects of dorsal root section or spinal transection. Brain Res 1985; 359: 152–7
Arai H, Emson PC. Regional distribution of neuropeptide K and other tachykinins (neurokinin A, neurokinin B and substance P) in rat central nervous system. Brain Res 1986; 399: 240–9
Moussaoui SM, Le Prado N, Faucher DC, et al. Distribution of neurokinin B in rat spinal cord and peripheral tissues: comparison with neurokinin A and substance P and effects of neonatal capsaicin treatment. Neuroscience 1992; 48: 969–78
Hanesch U, Heppelmann B, Schmidt RF. Neurokinin A-like immunoreactivily in articular afferents of the cat. Brain Res 1992; 586: 332–5
Fleetwood-Walker SM, Mitchell R, Hope PJ, et al. The involvement of neurokinin receptor subtypes in somatosensory processing in the superficial dorsal horn of the cat. Brain Res 1990; 519: 169–82
Salter MW, Henry JL. Responses of functionally identified neurones in the dorsal horn of the cat spinal cord to substance P. neurokinin A and physalaemin. Neuroscience 1991; 43: 601–10
Fleetwood-Walker SM, Parker RMC, Munro FE, et al. Evidence for a role of tachykinin NK2 receptors in mediating brief nociceptive inputs to rat dorsal horn (laminae III-V) neurons. Eur J Pharmacol 1993; 242: 173–81
Cridland RA, Henry JL. Comparison of the effects of substance P. neurokinin A. physalaemin and eledoisin in facilitating a nociceptive reflex in the rat. Brain Res 1986; 381: 93–9
Gamse R, Saria A. Nociceptive behavior after intrathecal injections of substance P, neurokinin A and calcitonin gene-related peptide in mice. Neurosci Lett 1986; 70: 143–7
Xu X-J, Wiesenfeld-Hallin Z. Intrathecal neurokinin A facilitates the spinal nociceptive flexor reflex evoked by thermal and mechanical stimuli and synergistically interacts with substance P. Acta Physiol Scand 1992; 144: 163–8
Linderoth B, Brodin E. Tachykinin release from rat spinal cord in vitro and in vivo in response to various stimuli. Regul Pept 1988; 21: 129–40
Laneuville O, Dorais J, Couture R. Characterization of the effects produced by neurokinins and three agonists selective for neurokinin receptor subtypes in a spinal nociceptive reflex of the rat. Life Sci 1988; 42: 1295–305
Hokfelt T, Vincent S, Hellsten L, et al. Immunohistochemical evidence for a ‘neurotoxic’ action of (D-Pro2, D-Trp7,9 )-substance P, an analogue with substance P antagonistic activity. Acta Physiol Scand 1981; 113: 571–3
Salt TE, De Vries GJ, Rodriguez RE, et al. Evaluation of [D-Pro2, D-Trp7,9]-substance P as an antagonist of substance P responses in the rat central nervous system. Neurosci Lett 1982; 30: 291–5
Post C, Paulsson I. Antinociceptive and neurotoxic actions of substance P analogues in the rat’s spinal cord after intrathecal administration. Neurosci Lett 1985; 57: 157–64
Matsumura H, Sakurada T, Hara A, et al. Intrathecal substance P analogue causes motor dysfunction in the rat. Neuropharmacology 1985; 24: 811–3
Wiesenfeld-Hallin Z, Duranti R. D-Arg1. D-Trp7–9, Leu11-sub-stance P (spantide) does not antagonize substance P induced hyperexcitability of the nociceptive flexion withdrawal reflex in the rat. Acta Physiol Scand 1987; 129: 55–9
Sakurada T, Hara A, Matsumura H, et al. A substance P analogue reduces amino acid contents in the rat spinal cord. Pharmacol Toxicol 1990; 66: 75–6
Snider RM, Constantine JW, Lowe III JA, et al. A potent nonpeptide antagonist of the substance P(NK1) receptor. Science 1991; 251: 435–7
McLean S, Ganong AH, Seeger T, et al. Activity and distribution of binding sites in brain of a nonpeptide substance P (NK1) receptor antagonist. Science 1991; 251: 437–9
Rouissi N, Gitter BD, Waters DC, et al. Selectivity and specificity of new, non-peptide. guinuclidine antagonists of substance P. Biochem Biophys Res Commun 1991; 176: 894–901
Håkanson R, Wang Z-Y, Folkers K. Comparison of spantide II and CP-96, 345 for blockade of tachykinin-evoked contractions of smooth muscle. Biochem Biophys Res Commun 1991; 178: 297–301
Lembeck F, Donnerer J, Tsuchiya M, et al. The non-peptide tachykinin antagonist, CP-96, 345. is a potent inhibitor of neurogenic inflammation. Br J Pharmacol 1992; 105: 527–30
Nagahisa A, Kanal Y, Suga O, et al. Anti-inflammatory and analgesic activity of a non-peptide substance P receptor antagonist. Eur J Pharmacol 1992; 217: 191–5
Birch PJ, Harrison SM, Hayes AG, et al. The non-peptide NK1 receptor antagonist. (±)-CP-96,345, produces antinociceptive and anti-oedema effects in the rat. Br J Pharmacol 1992; 105: 508–10
Vamamoto T, Yaksh TL. Stereospecific effects of a nonpeptidic NK1 selective antagonist. CP-96,345: antinoeiception in the absence of motor dysfunction. Life Sci 1991; 49: 1955–63
Sakurada T, Katsumata K, Yogo H, et al. Antinociception induced by CP-96, 345, a non-peptide NK1 receptor antagonist, in the mouse formalin and capsaicin tests. Neurosei Lett 1993; 151: 142–5
Leeci A, Giuliani S, Patacehini R, et al. Role of NK1 tachykinin receptors in thermonociception: effect of (±)-CP-96.345, a non-peptide substance P antagonist, on the hot plate test in mice. Neurosci Lett 1991; 129: 299–302
Sakurada T, Manome Y, Katsumata T, et al. Comparison of antagonistic effects of sendide and CP-96.345 on a spinally mediated behavioural response in mice. Eur J Pharmacol 1994; 261: 85–90
Dubuisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effect of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 1977; 4: 161–74
Abbott FV, Melzack R, Samuel C. Morphine analgesia in the tail-flick and formalin pain test is mediated by different neural systems. Exp Neurol 1982; 75: 644–51
Dickenson AH, Sullivan AF. Subcutaneous formal in-induced activity of dorsal horn neurones in the rat: differential response to an intrathecal opiate administered pre and post formalin. Pain 1987; 30: 349–60
Hunskaar S, Hole K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain 1987; 30: 103–14
Haley JE, Dickenson AH, Schachter M. Electrophysiological evidence for a role of bradykinin in chemical nociception in the rat. Neurosci Lett 1989; 97: 198–202
Shibata M, Ohkubo X Takahashi H, et al. Modified formalin test: characteristic biphasic pain response. Pain 1989; 38: 347–52
Xu XJ, Dalsgaard CJ, Wiesenfeld-Hallin Z. Intrathecal CP-96, 345 blocks reflex facilitation induced in rats by substance P and C-fiber-conditioning stimulation. Eur J Pharmacol 1992; 216: 337–44
Garret C, Carrette A, Fardin V, et al. Pharmacological properties of a potent and selective non-peptide substance P antagonist. Proc Natl Acad Sci USA 1991; 88: 10208–12
Rupniak NMJ, Boyce S, Williams AR, et al. Antinociceptive actions of NK1 receptor antagonists: non-specific effects of racemic RP-67, 580. Br J Pharmacol 1993; 110: 1607–13
Sakurada T, Katsumata K, Yogo H, et al. The neurokinin-1 receptor antagonist, sendide. exhibits antinociceptive activity in the formalin test. Pain 1995; 60: 175–80
Yashpal K, Radhakrishnan V, Coderre TJ, et al. CP-96, 345, but not its stereoisomer, CP-96, 345, blocks the nociceptive responses to intrathecally administered substance P and to noxious thermal and chemical stimuli in the rat. Neuroscience 1993; 52: 1039–47
Nagahisa A, Asai R, Kanai Y, et al. Non-specific activity of (±)-CP-96, 345 in models of pain and inflammation. Br J Pharmacol 1992; 107: 273–5
Schmidt AW, McLean S, Heym J. The substance P receptor antagonist CP-96, 345 interacts with Ca2+ channels. Eur J Pharmacol 1992; 215: 351–2
Guard S, Boyle SJ, Tang K-W, et al. The interaction of the NK1 receptor antagonist CP-96, 345 with L-type calcium channels and its functional consequences. Br J Pharmacol 1993; 110: 385–91
Miranda HF, Bustamame D, Kramer V, et al. Antinociceptive effects of Ca2+ channel blockers. Eur J Pharmacol 1992; 217: 137–41
McLean S, Ganong A, Seymour PA, et al. Pharmacology of CP-99.994: a nonpeptide antagonist of the tachykinin neurokinin-1 receptor. J Pharmacol Exp Ther 1993; 267: 472–9
Rosen T, Seegar TF, McLean S, et al. Synthesis, in vivo binding profile, and autoradiographic analysis of [3H]-cis-3-[(2-methoxybenzyl)amino]-2-phenylpiperidine. a highly potent and selective substance P receptor antagonist radioligand. J Med Chem 1993; 36: 3197–201
McLean S, Snider RM, Desai MC, et al. CP-99, 994. a nonpeptide antagonist of the tachykinin NK-1 receptors. Regul Pept 1993; 46: 329–31
Seguin L, Marouillr-Girardon SL, Millan MJ. Antinociceptive profiles of non-peptidergic neurokinin1 and neurokinin2 receptor antagonists: a comparison to other classes of antinociceptive agent. Pain 1995; 61: 325–43
Smith G, Harrison S, Bowers J, et al. Non-specific effect of the tachykinin NK1 receptor antagonist CP-99, 994 in antinociceptive tests in rat mouse and gerbil. Eur J Pharmacol 1994; 271: 481–7
Rupniak NMJ, Webb JK, Williams AR, et al. Antinociceptive activity of the tachykinin NK1 receptor antagonist CP-99.994, in conscious gerbils. Br J Pharmacol 1995; 116: 1937–43
Laird JMA, Hargreaves RJ, Hill RG. Effect of RP67580. a nonpeptide neurokinin-1 receptor antagonist, on facilitation of a nociceptive spinal flexion reflex in the rat. Br J Pharmacol 1993; 109: 713–8
Chapman V, Dickenson AH. The effect of intrathecal administration of RP 67580, a potent neurokinin 1 antagonist on nociceptive transmission in the rat spinal cord. Neurosci Lett 1993; 157: 149–52
Rupniak NMJ, Carlson E, Boyce S, et al. Enantioselective inhibition of the formalin paw late phase by the NK1 receptor antagonist L-733, 060 in gerbils. Pain 1996; 67: 189–95
Sakurada T, Yamada T, Tan-No K, et al. Differential effects of substance P analogs on neurokinin 1 receptor agonists in the mouse spinal cord. J Pharmacol Exp Ther 1991; 259: 205–10
Fong TM, Anderson SA, Yu H, et al. Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor. Mol Pharmacol 1992; 41: 24–30
Kage R, Leeman SE, Boyd ND. Biochemical characterization of two different forms of the substance P receptor in rat sub-maximary gland. J Neurochem 1993; 60: 347–51
Mantyh PW, Rogers SD, Ghilardi JR, et al. Differential expression of two isoforms of the neurokinin-1 (substance P) receptor in vivo. Brain Res 1996; 719: 8–13
Maggi CA, Eglezos A, Quartara L, et al. Heterogeneity of NK-2 tachykinin receptors in hamster and rabbit smooth muscles. Regul Pept 1992; 37: 85–93
Maggi CA, Giuliani S, Palaechini R, et al. Heterogeneity of tachykinin NK2 receptors in rabbit, guinea-pig and human smooth muscles. Neuropeptides 1992; 23: 181–6
Emonds-Alt X, Vilain P, Goulaouic P, et al. A potent and selective nonpeptide antagonist of the neurokinin A (NK-2) receptor. Life Sci 1992; 50: PL101–6
Advenier C, Rouissi N, Nguyen OT, et al. Neurokinin-A (NK-2) receptor revisited with SR 48968. a potent nonpeptide antagonist. Biochem Biophys Res Commun 1992; 184: 1418–24
Emonds-Alt X, Golliot F, Pointeau P, et al. Characterization of the binding sites of [3H]SR 48968. a potent nonpeptide radioligand antagonist of the neurokinin-2 receptor. Biochem Biophys Res Commun 1993; 191: 1172–7
Mantyh PW, Gates T, Mantyh CR, et al. Autoradiographic localization and characterization of tachykinin receptor binding sites in the rat brain and peripheral tissues. S Neurosci 1989; 9: 258–79
Tsuchida K, Shigemoto R, Yokota Y, et al. Tissue distribution and quantitation of the mRNA for three rat tachykinin receptors. Eur J Biochem 1990; 193: 751–7
Takeda Y, Krause JE. Pharmacological and molecular biological studies on the diversity of rat tachykinin NK-2 receptor subtypes in rat CNS, duodenum, vas deferens, and urinary bladder. Ann NY Acad Sci 1991; 632: 479–82
Xu H-J, Maggi CA, Wiesenfeld-Hallin Z. On the role of NK2 tachykinin receptors in the mediation of spinal reflex excitability in the rat. Neuroscience 1991; 44: 483–90
Urban L, Maggi CA, Nagy I, et al. The selective NK2 receptor antagonist MEN 10, 376 inhibits synaptic excitation of dorsal horn neurons evoked by C-fibre activation in the in vitro spinal cord [abstract]. Neuropeptides 1992; 22: 68
Nagy I, Maggi CA, Dray A, et al. The role of neurokinin and N-methyl-D-aspartate receptors in synaptic transmission from capsaicin-sensitive primary afferents in the rat spinal cord in vitro. Neuroscience 1993; 52: 1029–37
Thompson SWN. Dray A, Urban L. The contribution of tachykinin receptor activation to C-fibre-evoked response in the neonatal rat spinal cord in vitro [abstract]. J Physiol 1993; 459: 464P
Neugebauer V, Schaiblc H-G, Weiretter F, et al. The involvement of substance P and neurokinin-1 receptors in the response of rat dorsal horn neurons to noxious but not to innocuous mechanical stimuli applied to the knee joint. Eur J Pharmacol 1994; 666: 207–15
Neugebauer V, Rumenapp P, Schaible H-G. The role of spinal neurokinin-2 receptors in the processing of nociceptive information from the joint and in the generation and maintenance of inflammation-evoked hyperexcitability of dorsal horn neurons in the rat Eur J Neurosci 1996; 8: 249–60
Oku R, Satoh M, Takagi H. Release of substance P from the spinal dorsal horn is enhanced in polyarthritic rats. Neurosci Lett 1987; 74: 315–9
Schaible H-G, Jarrott B, Hope PJ, et al. Release of immunoreactive substance Pin the cat spinal cord during development of acute arthritis in cat’s knee: a study with antibody bearing microprobes. Brain Res 1990; 529: 214–23
Hope PJ, Jarrot B, Schaible H-G, et al. Release and spread of immunoreactive neurokinin A in the cat spinal cord in a model of acute arthritis. Brain Res 1990; 533: 292–9
Andrews PV, Helme RD, Thomas KL. NK1-receptor mediation of neurogenic plasma extravasation in the rat skin. Br J Pharmacol 1989; 97: 1232–8
Abelli L, Maggi CA, Rovero P, et al. Effect of synthetic tachykinin analogues on airway microvascular leakage in rats and guinea-pigs: evidence for the involvement of NK-1 receptors. J Auton Pharmacol 1991; 11: 267–75
Moussaoui SM, Montier F, Carruette A, et al. A non-peptide NK1-receptor antagonist, RP67580, inhibits neurogenic infiammation postsynaptically. Br J Pharmacol 1993; 109: 259–64
Emonds-Alt X, Doutremepuich J-D, Heaulme M, et al. In vitroand in vivo biological activities of SR 140333, a novel potent non-peptide tachykinin NK1 receptor antagonist. Eur J Pharmacol 1993; 250: 403–13
Jung M, Calassi R, Maruani J, et al. Neuropharmacological characterization of SR 140333. a non-peptide antagonist of NK1 receptors. Neuropharmacology 1994; 33: 167–79
Amann R, Schuligoi R, Holzer P, et al. The non-peptide NK1 receptor antagonist SR 140333 produces long-lasting inhibition of neurogenic inflammation, but does not influence acute chemo- or thermonociception in rats. Naunyn Schmiedebergs Arch Pharmacol 1995; 352: 201–5
Moskowitz MA. Neurogenic versus vascular mechanisms of sumatriptan and ergot alkaloids in migraine. Trends Pharmacol Sci 1992; 13: 307–11
Edvinsson L, Rosendal-Helgesen S, Uddman R. Substance P: localization, concentration and release in cerebral arteries, choroid plexus and dura mater. Cell Tissue Res 1983; 234: 1–7
Saito K, Liu-Chen L-Y, Moskowitz MA. Substance P-like immunoreactivity in rat forebrain leptomeninges and cerebral vessels originates from the trigeminal but not sympathetic ganglia. Brain Res 1987; 403: 66–71
Moskowitz MA, Buzzi MG. Neuroeffector functions of sensory fibres: implications for headache mechanisms and drug actions. J Neurol 1991; 238 Suppl. 1: S18–22
Buzzi MG, Moskowitz MA. The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater. Br J Pharmacol 1990; 99: 202–6
O’Shaughnessy CT, Connor HE. Neurokinin NK1 receptors mediate plasma protein extravasation in guinea-pig dura. Eur J Pharmacol 1993; 236: 319–21
Shepheard SL. Williamson DJ, Hill RG, et al. The non-peptide neurokinin1 receptor antagonist, RP 67580, blocks neurogenic plasma extravasation in the dura mater of rats, Br J Pharmacol 1993; 108: 11–2
Shepheard SL, Williamson DJ, Williams J, et al. Comparison of the effects of sumatriptan and the NK 1 antagonist CP-99, 994 on plasma extravasation in dura mater and e-fos mRN A expression in trigeminal nucleus caudalis of rats. Neuropharmacology 1995; 34: 255–61
Lee WS, Moussaoui SM, Moskoaitz MA. Blockade by oral or parenteral RPR 100893 (a non-peptide NK1 receptor antagonist) of neurogenic plasma protein extravasation within guinea-pig dura mater and conjunctiva. Br J Pharmacol 1994; 112: 920–4
Morimoto H, Murai M, Maeda Y, et al. FK224, a novel cyclopeptide substance P antagonist with NK1 and NK2 receptor selectivity. J Pharmacol Exp Ther 1992; 262: 398–402
Murai M, Morimoto H, Maeda Y, et al. Effects of FK224, a novel compound NK1 and NK2 receptor antagonist, on airway constriction and airway edema induced by tachykinins and sensory nerve stimulation in guinea-pigs. J Pharmacol Exp Ther 1992; 262: 403–8
Ronineau P, Lonchampt M, Kucharczk N, et al. In vitro and in vivopharmacology of S 16474, a novel dual tachykinin NK1 and NK2 receptor antagonist. Eur J Pharmacol 1995; 294: 677–84
Kudlacz EM, Shatzer S, Knioppenberg RW, et al. In vitro and in vivo characterization of MDL 105, 212. a nonpeptide NK-1/NK-2 receptor antagonist J Pharmacol Exp Ther 1996; 277: 840–51
Post C, Folkers K. Behavioural and antinociceptive effects of intrathecally injected substance P analogues in mice. Eur J Pharmacol 1985; 113: 335–43
Sakurada T, Manome Y, Katsumata H, et al. Naloxone-reversible effect of spantide on the spinally mediated behavioural response induced by neurokinin-2 and -3 receptor agonists. Naunyn Schmiedebergs Arch Pharmacol 1992; 346: 69–75
Tan-No K, Sakurada T, Yamada T, et al. Spantide-induced antinociception in the opioid mechanism. Regul Pept 1993; 46: 343–5
Sakurada T, Manome Y, Tan-No K, et al. A selective and extremely potent antagonist of the neurokinin-1 receptor. Brain Res 1992; 593: 319–22
Beresford IJM, Birch PJ, Hagan RM, et al. Investigation into species variants in tachykinin NK-1 receptors by use of the nonpeptide antagonist CP 96345. Br J Pharmacol 1991; 104: 292–3
Gitter BD, Waters DC, Bruns RE et al. Species differences in affinities of nonpeptide antagonists for substance P receptors. Eur J Pharmacol 1991; 197: 237–8
Fardin V, Foucault F, Bock MD. et al. Binding profile of RP 67, 580. a new nonpeptide SP antagonist: comparison with CP 96, 345 [abstract]. Br J Pharmacol 1992; 105: 80P
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sakurada, T., Sakurada, C., Tan-No, K. et al. Neurokinin Receptor Antagonists. CNS Drugs 8, 436–447 (1997). https://doi.org/10.2165/00023210-199708060-00002
Published:
Issue Date:
DOI: https://doi.org/10.2165/00023210-199708060-00002