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Chemical Compound Review:

SureCN678696 (2R,3S)-1-[[2-methoxy-5...

Synonyms: AG-D-89772, KB-62486, CTK4C4679, DNC000470, LS-113868, ...

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Disease relevance of Cp 122721

RESULTS: In the initial dose-ranging study, only 10% of the patients experienced emesis within the first 8 h after surgery with CP-122,721 200 mg compared with 50% in the placebo group [1].
In addition, the median times for 75% of patients to remain free from postoperative nausea and vomiting were 82, 75, and 362 min in the ondansetron, CP-122,721, and combination groups, respectively [1].
In addition, consistent with insurmountable blockade observed in vitro, CP-122,721 (0.01, 0.03 0.3 mg/kg, p.o.) produced a rightward shift in the dose response curve for SP-induced hypotension in the awake dog that was accompanied by a decrease in the maximal response [2].

Psychiatry related information on Cp 122721

In vivo, CP-122,721 potently blocked plasma extravasation in guinea pig lung elicited by aerosolized capsaicin (1 mM) with an ID50 = 0.01 mg/kg, p.o. Orally administered CP-122,721 antagonized Sar9, Met (O2)11-SP-induced locomotor activity in guinea pigs with an ID50 = 0.2 mg/kg suggesting good entry into the central nervous system [2].

High impact information on Cp 122721

The aim of the present study was to determine whether oral (p.o.) administration of the NK1 receptor antagonists MK-869, L-742,694, L-733,060, CP-99,994, and CP-122,721 produced anxiolytic-like effects in the gerbil elevated plus-maze [3].
In the interaction study, 6% of the patients receiving CP-122,721 200 mg orally experienced emesis less than 2 h after surgery compared with 17% with ondansetron alone [1].
CONCLUSIONS: Oral CP-122,721 200 mg decreased emetic episodes compared with ondansetron (4 mg intravenously) during the first 24 h after gynecologic surgery; however, there was no difference in patient satisfaction [1].
Characterization of CP-122,721; a nonpeptide antagonist of the neurokinin NK1 receptor [2].
CP-122,721 blocked SP-induced excitation of locus ceruleus cells in guinea pig brain slices with a IC50 value of 7 nM [2].

Biological context of Cp 122721

This study investigated the effects of long-term daily CP-122,721 treatment on gene expression of SP and the NK-1R in the striatum and hindbrain of the rat [4].
Metabolism, pharmacokinetics and excretion of a potent tachykinin NK1 receptor antagonist (CP-122,721) in rat: characterization of a novel oxidative pathway [5].
The major metabolic pathways of CP-122,721 were due to O-demethylation, aromatic hydroxylation and indirect glucuronidation [5].
Synthesis and structure-activity relationships of CP-122,721, a second-generation NK-1 receptor antagonist [6].

Anatomical context of Cp 122721

Results show that treatment with CP-122,721 significantly increased SP-encoding mRNA and NK-1R mRNA levels in the striatum, but not in the hindbrain [4].

Gene context of Cp 122721

Selective antagonists for the NK-1R such as CP-122,721 block NK-1R-mediated responses both in vitro and in vivo [4].
These data support the hypothesis that CP-122,721 blocks emesis by a specific action at tachykinin NK1 receptors [7].
On the other hand, CP-122,721, a NK1-receptor antagonist, significantly reduced the emetic episodes to all four stimuli [8].

Analytical, diagnostic and therapeutic context of Cp 122721

The metabolism, pharmacokinetics and excretion of a potent and selective substance P receptor antagonist, (+)-(2S,3S)-3-(2-methoxy-5-trifluoromethoxybenzlamino)-2-phenylpiperidine, CP-122,721, have been studied in rat following oral administration of a single dose of [14C]CP-122,721 [5].

References

Substance P (Neurokinin-1) antagonist prevents postoperative vomiting after abdominal hysterectomy procedures. Gesztesi, Z., Scuderi, P.E., White, P.F., Wright, W., Wender, R.H., D'Angelo, R., Black, L.S., Dalby, P.L., MacLean, D. Anesthesiology (2000) [Pubmed]
Characterization of CP-122,721; a nonpeptide antagonist of the neurokinin NK1 receptor. McLean, S., Ganong, A., Seymour, P.A., Bryce, D.K., Crawford, R.T., Morrone, J., Reynolds, L.S., Schmidt, A.W., Zorn, S., Watson, J., Fossa, A., DePasquale, M., Rosen, T., Nagahisa, A., Tsuchiya, M., Heym, J. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
The gerbil elevated plus-maze II: anxiolytic-like effects of selective neurokinin NK1 receptor antagonists. Varty, G.B., Cohen-Williams, M.E., Morgan, C.A., Pylak, U., Duffy, R.A., Lachowicz, J.E., Carey, G.J., Coffin, V.L. Neuropsychopharmacology (2002) [Pubmed]
Chronic non-peptide neurokinin receptor antagonist treatment alters striatal tachykinin peptide and receptor gene expression in the rat. McCarson, K.E., Krause, J.E., McLean, S. Neurosci. Lett. (1998) [Pubmed]
Metabolism, pharmacokinetics and excretion of a potent tachykinin NK1 receptor antagonist (CP-122,721) in rat: characterization of a novel oxidative pathway. Kamel, A., Davis, J., Potchoiba, M.J., Prakash, C. Xenobiotica (2006) [Pubmed]
Synthesis and structure-activity relationships of CP-122,721, a second-generation NK-1 receptor antagonist. Rosen, T.J., Coffman, K.J., McLean, S., Crawford, R.T., Bryce, D.K., Gohda, Y., Tsuchiya, M., Nagahisa, A., Nakane, M., Lowe, J.A. Bioorg. Med. Chem. Lett. (1998) [Pubmed]
Broad spectrum antiemetic effects of CP-122,721, a tachykinin NK1 receptor antagonist, in ferrets. Gonsalves, S., Watson, J., Ashton, C. Eur. J. Pharmacol. (1996) [Pubmed]
Diphenidol has no actual broad antiemetic activity in dogs and ferrets. Nakayama, H., Yamakuni, H., Nakayama, A., Maeda, Y., Imazumi, K., Matsuo, M., Mutoh, S. J. Pharmacol. Sci. (2004) [Pubmed]

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