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Chemical Compound Review

CHEMBL135022     (2R)-N-[(2- methoxyphenyl)methyl]-2- phenyl...

Synonyms: SureCN14513344, CHEBI:323209, DNC000478, LS-113866, PDSP2_001709, ...
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Disease relevance of CP 99994


Psychiatry related information on CP 99994


High impact information on CP 99994

  • In initial experiments, this second phase was attenuated by 1-10 mg of the NK-1 receptor antagonist CP-99,994, given subcutaneously 10, 30, or 60 min before formalin (n = 8-10) and by 20 microgram given intrathecally 20 min after formalin (n = 13); the inactive isomer CP-100,263 was ineffective [8].
  • Bronchoconstriction induced by a submaximum dose of citric acid (10 breaths) was partially reduced by the administration of HOE 140, SR 48968, or the NK1 receptor antagonist CP-99,994 (8 micromol x kg-1, intravenous) alone and completely abolished by the combination of SR 48968 and CP-99,994 [9].
  • Although CP-99,994 infusion markedly attenuated the bronchoconstrictor response to the saline challenge in two subjects, it did not significantly decrease the area under curves obtained for SRaw and cough during saline challenge for the group as a whole (p = 0.9 for SRaw;p = 0.8 for cough) [10].
  • The NTS microinjection of a NK1 antagonist (CP-99,994) in vivo attenuated the tachycardic response to hindlimb pinch [11].
  • 5. The potentiating action of ANGII on the chemoreceptor reflex cardiac response was abolished by a neurokinin type 1 (NK1) receptor blocker (CP-99,994, 5 microM) but this had no effect on the baroreceptor reflex [12].

Chemical compound and disease context of CP 99994

  • 4. With a cisplatin (5 mg kg-1) emetogenic challenge, administration of CP 99,994 (10 mg kg-1) at 8 hourly intervals, the first injection being administered 30 s post cisplatin, was associated with 4 or more abolitions of emesis during both the acute and delayed phase [2].
  • The less active enantiomer of CP-99,994, CP-100,263 (10 mg/kg), did not alter raclopride-induced catalepsy [3].
  • Enantiospecific inhibition of emesis induced by nicotine in the house musk shrew (Suncus murinus) by the neurokinin1 (NK1) receptor antagonist CP-99,994 [13].
  • Ondansetron was inactive to modify behavior, but CP-99,994 reduced spontaneous locomotor activity and lip licking by 48% (P<0.01) and 79% (P<0.01), respectively; CP-99,994 also abolished spontaneous burrowing activity (P<0.05) [14].
  • The emesis was antagonized significantly (P<0.05) by ondansetron (0.3 and 1 mg/kg, i.p.) and (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenlypiperidine hydrochloride (CP-99,994; 10 mg/kg, i.p.), but neither compound reduced defecations and/or tenesmus, with ondansetron (0.3 mg/kg) actually producing a slight increase (P<0.05) [15].

Biological context of CP 99994

  • We conclude that administration of 250 micrograms/kg of CP-99,994 over 2 h does not significantly inhibit hypertonic saline-induced bronchoconstriction or cough in subjects with mild asthma and does not have acute bronchodilator activity in these subjects [10].
  • The NK(3) receptor endocytosis was blocked by SR-142801 but not by CP-99994 [16].
  • 2. CP-99994 displaced [3H]-substance P from cat cortex with IC50 of 0.52 +/- 0.08 nM [17].
  • In addition, ODQ (1 microM) increased the electrically-evoked tachykininergic and cholinergic muscle contractions as measured in the presence of scopolamine (100 nM) or of the neurokinin-1 receptor antagonist CP 99994 (100 nM), respectively [18].
  • A new NK1 receptor antagonist (CP-99,994) prevents the increase in tracheal vascular permeability produced by hypertonic saline [19].

Anatomical context of CP 99994


Associations of CP 99994 with other chemical compounds

  • This effect was reduced by two different NK1 receptor antagonists, CP-99,994 and SR 140333 [23].
  • This baroreceptor reflex depression was mimicked by NTS microinjection of substance P and antagonized by microinjection of either bicuculline (a GABAA receptor antagonist) or a neurokinin type 1 (NK1) receptor antagonist (CP-99994) [24].
  • 4. Under conditions where the guinea-pig lung parenchymal NK1 receptor was fully occupied by a saturating concentration of either [Sar9Met(O2)11]substance P (1 microM) or CP-99,994 (2.7 microM), residual [125I]-neurokinin A specific binding was inhibited in a concentration-dependent manner by both [beta Ala8]neurokinin A and SR48968 [25].
  • 1. The anti-emetic effects of the NK1 tachykinin receptor antagonist, CP 99,994 (10 mg kg-1) were investigated in the ferret using a cisplatin-induced acute (day 1) and delayed (day 2 and 3) retching and vomiting model [2].
  • In the presence of the non-peptide NK1 antagonists, CP-99,994 and RP67580, and the peptide antagonist, GR82334, the current-response relationship was reversibly shifted to the right [26].

Gene context of CP 99994


Analytical, diagnostic and therapeutic context of CP 99994

  • CP-99,994 produced analgesia that was significant at 90 minutes (P < 0.01 compared with placebo), but not at subsequent time points [1].
  • Both systemic administration and intrastriatal perfusion of CP-99,994 alone decreased striatal ACh release [3].
  • 2. A neurokinin1 (NK1) receptor antagonist (CP-99,994, 10 mM) had no effect on the paw withdrawal latency when it was administered spinally through a microdialysis fibre before the induction of inflammation [32].
  • 4. CP-99,994 (1 mg kg-1, i.v.) blocked retching induced by electrical stimulation of the ventral abdominal vagus without affecting the cardiovascular response, the apnoeic response to central vagal stimulation or the guarding and hypertensive response to stimulation of the greater splanchnic nerves [22].
  • From extracellular recordings of cardioreceptive NTS neurons, CP-99,994 reduced reversibly the total number of evoked spikes, peak firing frequency and response duration evoked by intraventricular injections of veratridine (n = 5) or bradykinin (n = 5) [4].


  1. The substance P receptor antagonist CP-99,994 reduces acute postoperative pain. Dionne, R.A., Max, M.B., Gordon, S.M., Parada, S., Sang, C., Gracely, R.H., Sethna, N.F., MacLean, D.B. Clin. Pharmacol. Ther. (1998) [Pubmed]
  2. The action of the NK1 tachykinin receptor antagonist, CP 99,994, in antagonizing the acute and delayed emesis induced by cisplatin in the ferret. Rudd, J.A., Jordan, C.C., Naylor, R.J. Br. J. Pharmacol. (1996) [Pubmed]
  3. The neurokinin1 receptor antagonist CP-99,994 reduces catalepsy produced by the dopamine D2 receptor antagonist raclopride: correlation with extracellular acetylcholine levels in striatum. Anderson, J.J., Randall, S., Chase, T.N. J. Pharmacol. Exp. Ther. (1995) [Pubmed]
  4. Importance of neurokinin-1 receptors in the nucleus tractus solitarii of mice for the integration of cardiac vagal inputs. Paton, J.F. Eur. J. Neurosci. (1998) [Pubmed]
  5. Substance P and capsaicin-induced mechanical hyperalgesia in the rat knee joint; the involvement of bradykinin B1 and B2 receptors. Davis, A.J., Perkins, M.N. Br. J. Pharmacol. (1996) [Pubmed]
  6. Pharmacology of CP-99,994; a nonpeptide antagonist of the tachykinin neurokinin-1 receptor. McLean, S., Ganong, A., Seymour, P.A., Snider, R.M., Desai, M.C., Rosen, T., Bryce, D.K., Longo, K.P., Reynolds, L.S., Robinson, G. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
  7. Effect of intrathecal pretreatment with the neurokinin receptor antagonist CP-99994 on the expression of naloxone-precipitated morphine withdrawal symptoms. Buccafusco, J.J., Shuster, L.C. Brain Res. Bull. (1997) [Pubmed]
  8. Evidence for tonic activation of NK-1 receptors during the second phase of the formalin test in the Rat. Henry, J.L., Yashpal, K., Pitcher, G.M., Chabot, J., Coderre, T.J. J. Neurosci. (1999) [Pubmed]
  9. Bronchoconstriction induced by citric acid inhalation in guinea pigs: role of tachykinins, bradykinin, and nitric oxide. Ricciardolo, F.L., Rado, V., Fabbri, L.M., Sterk, P.J., Di Maria, G.U., Geppetti, P. Am. J. Respir. Crit. Care Med. (1999) [Pubmed]
  10. Effect of an NK1 receptor antagonist (CP-99,994) on hypertonic saline-induced bronchoconstriction and cough in male asthmatic subjects. Fahy, J.V., Wong, H.H., Geppetti, P., Reis, J.M., Harris, S.C., Maclean, D.B., Nadel, J.A., Boushey, H.A. Am. J. Respir. Crit. Care Med. (1995) [Pubmed]
  11. Nociception attenuates parasympathetic but not sympathetic baroreflex via NK1 receptors in the rat nucleus tractus solitarii. Pickering, A.E., Boscan, P., Paton, J.F. J. Physiol. (Lond.) (2003) [Pubmed]
  12. Differential effects of angiotensin II on cardiorespiratory reflexes mediated by nucleus tractus solitarii - a microinjection study in the rat. Paton, J.F., Kasparov, S. J. Physiol. (Lond.) (1999) [Pubmed]
  13. Enantiospecific inhibition of emesis induced by nicotine in the house musk shrew (Suncus murinus) by the neurokinin1 (NK1) receptor antagonist CP-99,994. Tattersall, F.D., Rycroft, W., Marmont, N., Cascieri, M., Hill, R.G., Hargreaves, R.J. Neuropharmacology (1995) [Pubmed]
  14. Action of ondansetron and CP-99,994 to modify behavior and antagonize cisplatin-induced emesis in the ferret. Lau, A.H., Kan, K.K., Lai, H.W., Ngan, M.P., Rudd, J.A., Wai, M.K., Yew, D.T. Eur. J. Pharmacol. (2005) [Pubmed]
  15. Differential action of anti-emetic drugs on defecation and emesis induced by prostaglandin E2 in the ferret. Kan, K.K., Rudd, J.A., Wai, M.K. Eur. J. Pharmacol. (2006) [Pubmed]
  16. Independent endocytosis of the NK(1) and NK(3) tachykinin receptors in neurons of the rat myenteric plexus. Jenkinson, K.M., Mann, P.T., Southwell, B.R., Furness, J.B. Neuroscience (2000) [Pubmed]
  17. The effect of CP-99994 on the responses to provocative motion in the cat. Lucot, J.B., Obach, R.S., McLean, S., Watson, J.W. Br. J. Pharmacol. (1997) [Pubmed]
  18. Nitric oxide-sensitive guanylyl cyclase inhibits acetylcholine release and excitatory motor transmission in the guinea-pig ileum. Hebeiss, K., Kilbinger, H. Neuroscience (1998) [Pubmed]
  19. A new NK1 receptor antagonist (CP-99,994) prevents the increase in tracheal vascular permeability produced by hypertonic saline. Piedimonte, G., Bertrand, C., Geppetti, P., Snider, R.M., Desai, M.C., Nadel, J.A. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
  20. Differences in the effects of NK1-receptor antagonists, (+/-)-CP 96,345 and CP 99,994, on agonist-induced responses in guinea-pig trachea. Longmore, J., Razzaque, Z., Shaw, D., Hill, R.G. Br. J. Pharmacol. (1994) [Pubmed]
  21. Antagonism of nociceptive responses of cat spinal dorsal horn neurons in vivo by the NK-1 receptor antagonists CP-96,345 and CP-99,994, but not by CP-96,344. Radhakrishnan, V., Henry, J.L. Neuroscience (1995) [Pubmed]
  22. The anti-emetic effects of CP-99,994 in the ferret and the dog: role of the NK1 receptor. Watson, J.W., Gonsalves, S.F., Fossa, A.A., McLean, S., Seeger, T., Obach, S., Andrews, P.L. Br. J. Pharmacol. (1995) [Pubmed]
  23. NK1 receptor stimulation causes contraction and inositol phosphate increase in medium-size human isolated bronchi. Amadesi, S., Moreau, J., Tognetto, M., Springer, J., Trevisani, M., Naline, E., Advenier, C., Fisher, A., Vinci, D., Mapp, C., Miotto, D., Cavallesco, G., Geppetti, P. Am. J. Respir. Crit. Care Med. (2001) [Pubmed]
  24. Somatic nociception activates NK1 receptors in the nucleus tractus solitarii to attenuate the baroreceptor cardiac reflex. Boscan, P., Kasparov, S., Paton, J.F. Eur. J. Neurosci. (2002) [Pubmed]
  25. Identification of both NK1 and NK2 receptors in guinea-pig airways. McKee, K.T., Millar, L., Rodger, I.W., Metters, K.M. Br. J. Pharmacol. (1993) [Pubmed]
  26. Inhibition of Ca(2+)-sensitive K+ currents in NG 108-15 cells by substance P and related tachykinins. Phenna, S., Carpenter, E., Peers, C., Maudsley, S., Gent, J.P. Br. J. Pharmacol. (1996) [Pubmed]
  27. Comparison of cardiorespiratory reflexes in NK1 receptor knockout, heterozygous and wild-type mice in vivo. Butcher, J.W., De Felipe, C., Smith, A.J., Hunt, S.P., Paton, J.F. J. Auton. Nerv. Syst. (1998) [Pubmed]
  28. Neurokinin receptors (NK1, NK2) in the mouse: a pharmacological study. Nsa Allogho, S., Nguyen-Le, X.K., Gobeil, F., Pheng, L.H., Regoli, D. Can. J. Physiol. Pharmacol. (1997) [Pubmed]
  29. Acute and chronic effects of capsaicin in perfused rat muscle: the role of tachykinins and calcitonin gene-related peptide. Griffiths, C.D., Geraghty, D.P., Eldershaw, T.P., Colquhoun, E.Q. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  30. Antinociceptive activity of the tachykinin NK1 receptor antagonist, CP-99,994, in conscious gerbils. Rupniak, N.M., Webb, J.K., Williams, A.R., Carlson, E., Boyce, S., Hill, R.G. Br. J. Pharmacol. (1995) [Pubmed]
  31. Activity of nonpeptide tachykinin antagonists on neurokinin a induced contractions in dog urinary bladder. Rizzo, C.A., Hey, J.A. J. Urol. (2000) [Pubmed]
  32. Differential roles of neurokinin 1 and neurokinin 2 receptors in the development and maintenance of heat hyperalgesia induced by acute inflammation. Sluka, K.A., Milton, M.A., Willis, W.D., Westlund, K.N. Br. J. Pharmacol. (1997) [Pubmed]
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