RP 67580Potent and selective NK1 antagonist CAS# 135911-02-3 |
- Perindopril Erbumine
Catalog No.:BCC3586
CAS No.:107133-36-8
- Losartan Potassium (DuP 753)
Catalog No.:BCC1080
CAS No.:124750-99-8
- Candesartan
Catalog No.:BCC2558
CAS No.:139481-59-7
- Telmisattan
Catalog No.:BCC3863
CAS No.:144701-48-4
- Imidapril HCl
Catalog No.:BCC3792
CAS No.:89396-94-1
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 135911-02-3 | SDF | Download SDF |
PubChem ID | 107686 | Appearance | Powder |
Formula | C29H30N2O2 | M.Wt | 438.57 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | Soluble to 100 mM in ethanol and to 50 mM in DMSO | ||
Chemical Name | (3aR,7aR)-2-[2-(2-methoxyphenyl)ethanimidoyl]-7,7-diphenyl-1,3,3a,5,6,7a-hexahydroisoindol-4-one | ||
SMILES | COC1=CC=CC=C1CC(=N)N2CC3C(C2)C(CCC3=O)(C4=CC=CC=C4)C5=CC=CC=C5 | ||
Standard InChIKey | VWBOQFANCXZMAU-LOSJGSFVSA-N | ||
Standard InChI | InChI=1S/C29H30N2O2/c1-33-27-15-9-8-10-21(27)18-28(30)31-19-24-25(20-31)29(17-16-26(24)32,22-11-4-2-5-12-22)23-13-6-3-7-14-23/h2-15,24-25,30H,16-20H2,1H3/t24-,25+/m0/s1 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Potent and selective tachykinin NK1 receptor antagonist (Ki values are 2.9 nM and > 10 μM for rat NK1, and rat NK2 and NK3 receptors respectively). Displays higher affinity at rat and mouse than human receptors. Antinociceptive in vivo, possibly partly via inhibition of calcium channels. |
RP 67580 Dilution Calculator
RP 67580 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.2801 mL | 11.4007 mL | 22.8014 mL | 45.6028 mL | 57.0034 mL |
5 mM | 0.456 mL | 2.2801 mL | 4.5603 mL | 9.1206 mL | 11.4007 mL |
10 mM | 0.228 mL | 1.1401 mL | 2.2801 mL | 4.5603 mL | 5.7003 mL |
50 mM | 0.0456 mL | 0.228 mL | 0.456 mL | 0.9121 mL | 1.1401 mL |
100 mM | 0.0228 mL | 0.114 mL | 0.228 mL | 0.456 mL | 0.57 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
- Lupinol C
Catalog No.:BCN4809
CAS No.:135905-53-2
- H-D-Asp(OtBu)-OtBu.HCl
Catalog No.:BCC2898
CAS No.:135904-71-1
- Blumenol C glucoside
Catalog No.:BCN6189
CAS No.:135820-80-3
- erythro-Guaiacylglycerol beta-dihydroconiferyl ether
Catalog No.:BCN7025
CAS No.:135820-77-8
- Koumine
Catalog No.:BCN6190
CAS No.:1358-76-5
- Isoforsythiaside
Catalog No.:BCN5413
CAS No.:1357910-26-9
- Boc-Glu(OBzl)-OH
Catalog No.:BCC3389
CAS No.:13574-13-5
- RGFP966
Catalog No.:BCC3991
CAS No.:1357389-11-7
- Nonin A
Catalog No.:BCN7149
CAS No.:1357351-29-1
- OG-L002
Catalog No.:BCC4549
CAS No.:1357302-64-7
- Taxinine M
Catalog No.:BCN6942
CAS No.:135730-55-1
- Palonosetron hydrochloride
Catalog No.:BCN2171
CAS No.:135729-62-3
- SR 2211
Catalog No.:BCC6310
CAS No.:1359164-11-6
- Caulophylline B
Catalog No.:BCN7499
CAS No.:1359978-55-4
- Phenazopyridine HCl
Catalog No.:BCC4698
CAS No.:136-40-3
- Tetracaine HCl
Catalog No.:BCC4399
CAS No.:136-47-0
- Ranaconitine
Catalog No.:BCN3870
CAS No.:1360-76-5
- AVL-292 benzenesulfonate
Catalog No.:BCC1386
CAS No.:1360053-81-1
- Angiotensin III (human, mouse)
Catalog No.:BCC1031
CAS No.:13602-53-4
- (1R,2S)-1-Amino-2-indanol
Catalog No.:BCC8381
CAS No.:136030-00-7
- Fmoc-Tic-OH
Catalog No.:BCC3341
CAS No.:136030-33-6
- Schisanlactone E
Catalog No.:BCN2593
CAS No.:136040-43-2
- Fmoc-Cys(pMeBzl)-OH
Catalog No.:BCC3476
CAS No.:136050-67-4
- Justiciresinol
Catalog No.:BCN3419
CAS No.:136051-41-7
The neurokinin-1 receptor antagonist RP 67580 reduces the sensitization of primary afferents by substance P in the rat.[Pubmed:11394924]
Eur J Pain. 2001;5(1):69-79.
The inflammatory mediator substance P (SP) produces a variety of biological effects in several tissues by binding to the tachykinin receptor neurokinin 1 (NK1) and, to a lesser extent, by binding to the neurokinin 2 receptor (NK2). To assess the sensitizing effect of SP on articular afferent fibres the NK1receptor antagonist RP 67580 was applied in normal and acutely inflamed rat knee joints. Altogether 38 fine afferent nerve fibres from the rat knee with conduction velocities of 0.71-13.5 m/s were recorded as single units, during non-noxious and noxious joint rotations. SP, injected i.a. as a bolus close to the knee joint, was able to sensitize 45.5% (10 of 22) of the units recorded from normal joints and 33.3% (five of 15) of afferents from inflamed joints. The following i.a. application of RP 67580 in a range of 20-200 nmol antagonized in a dose-dependent manner the sensitizing effect of SP in a large proportion of slowly conducting articular afferents from normal (66.7%) and inflamed (46.2%) knee joints. Subsequent SP application enhanced the afferent sensitivity further. The electrophysiological results presented here further support the suggestion that the sensitization of afferents by SP in the rat knee joint is mediated mainly by the NK1 receptor, which is probably located on the primary afferents.
A substance P antagonist, RP-67,580, ameliorates a mouse meningoencephalitic response to Trypanosoma brucei brucei.[Pubmed:9108123]
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4167-70.
Mice infected with the protozoan parasite Trypanosoma brucei brucei and treated subcuratively with the trypanocidal drug diminazene aceturate develop an acute inflammatory meningoencephalitis with associated astrocytic proliferation. This reaction is very similar to that seen in the fatal posttreatment reactive encephalopathies that can occur in human African trypanosomiasis. The 11-amino acid neuropeptide substance P (SP) has recently been identified as a mediator in many inflammatory responses, and the development of potent, highly specific, nonpeptide SP antagonists has provided a new opportunity to investigate the possible involvement of SP in a variety of pathological conditions. We therefore postulated that SP may play a role in the development of the posttreatment inflammatory encephalopathy found in this experimental mouse model of African trypanosomiasis. In the present study RP-67,580, a SP antagonist that binds specifically to NK-1 receptors, was given intraperitoneally at a dose of 2 mg/kg twice daily to mice in which a severe meningoencephalitis had been produced. A significant reduction in both the severity of the inflammatory response (P = 0.0001) as well as the degree of astrocyte activation (P < 0.001) was found in the brains of these animals as compared with control mice that had not received RP-67,580. An inactive enantiomer of this SP antagonist, RP-68,651, had no effect on the central nervous system inflammatory reaction. We conclude from these findings that the neuropeptide SP plays a key role in the development of the severe central nervous system inflammatory response associated with African trypanosomiasis.
The in vitro effect of substance P on the GnRH-induced LH release depends on the steroidal environment and is reverted by a NK1 receptor antagonist (RP 67580) in the cycling female rat.[Pubmed:9639246]
Neuropeptides. 1998 Apr;32(2):97-101.
A previously study reported that administration of substance P on the morning of the proestrous day induces an inhibition of afternoon gonadotropin preovulatory surges in the female rat. It has also been shown, with a non-peptide specific antagonist of the neurokinin 1 (NK1) receptor (RP 67580), that this effect is mediated by NK1 receptors. The present study used perifused anterior pituitaries from proestrous morning female rats and showed that the SP modulation of the GnRH-induced LH release is markedly dependent on the steroidal environment. In the absence of steroids or in the presence of 17beta estradiol, or a combination of 17beta estradiol and progesterone, SP inhibited the GnRH-induced LH release. In contrast, SP stimulated the GnRH-induced LH secretion in the presence of progesterone alone. However, the inhibitory or stimulatory effect of SP was antagonized by the specific NK1 receptor antagonist RP 67580.
The tachykinin NK-1 receptor antagonist, RP-67580, infused into the ventral tegmental area prevents stress-induced analgesia in the formalin test.[Pubmed:10386919]
Physiol Behav. 1999 Jun;66(4):717-21.
Substance P (SP) receptors in the ventral tegmental area (VTA) play a critical role in mediating the stress-induced activation of midbrain ascending dopamine (DA) neurons. Interestingly, SP acting in the VTA induces analgesia in the formalin test for tonic pain. Because exposure to stress inhibits pain in this test, we speculated that SP receptors in the VTA might mediate stress-induced analgesia. The present study explored this idea by examining the effect of blocking tachykinin NK-1 receptors in the VTA on footshock stress-induced analgesia in the formalin test. Intra-VTA infusions of the novel tachykinin NK-1 receptor antagonist, RP-67580, prevented this response. This finding suggests that exposure to stress inhibits tonic pain through the release of endogenous SP in the VTA.
Higher potency of RP 67580, in the mouse and the rat compared with other nonpeptide and peptide tachykinin NK1 antagonists.[Pubmed:7682138]
Br J Pharmacol. 1993 Mar;108(3):793-800.
1. This study was undertaken to compare the potency and selectivity of the nonpeptide (RP 67580, (+/-)-CP-96,345 and its chloro-derivative [(+/-)-cis-3-(2-chlorobenzylamino)-2-benzhydrylquinuclidine] (CP-C1)) and peptide (GR 71,251 and spantide) neurokinin1 (NK1) antagonists in mouse and rat preparations. 2. Among the NK1 antagonists tested, RP 67580 was the most potent in inhibiting the specific binding of [125I]-Bolton Hunter substance P ([125I]-BHSP) to crude synaptosomes from the rat brain (Ki: 2.9 nM). (+/-)-CP-96,345 was about ten fold less potent (Ki: 31 nM) than RP 67580 while other compounds exhibited even less affinity. 3. All NK1 antagonists inhibit competitively the activation of phospholipase C by [Pro9]substance P ([Pro9]SP) in cultured cortical astrocytes from the newborn mouse, a preparation rich in NK1 receptors but devoid of NK2 and NK3 receptors. pA2 values for the most potent compounds, RP 67580 and (+/-)-CP-96,345, were 8.28 and 7.08 respectively. When used alone, all antagonists showed some agonist activity at 10(-5) M, except spantide which was already effective at 10(-6) M. 4. An excellent correlation was found between the potency of the NK1 antagonists in blocking the stimulation by [Pro9]SP of phosphoinositide breakdown in cortical astrocytes and in inhibiting [125I]-BHSP specific binding to rat brain synaptosomes. 5. As shown on single cells by use of the Indo-1 microfluorometric method, RP 67580 (10(-7) M) prevented reversibly the elevation of cytosolic calcium concentration induced by [Pro9]SP (10(-8) M) in cultured cortical astrocytes. 6. Several experiments indicated that the antagonists were highly selective for NK1 receptors. RP 67580 did not modify the noradrenaline-evoked activation of phospholipase C in cortical astrocytes; when used at 10-5 M all antagonists had no or only little affinity for NK2 or NK3 binding sites and did not block the NKA (10-8 M)-induced activation of phospholipase C in the hamster urinary bladder (a selectiveNK2 test).7. In conclusion, RP 67580 appears to be a potent NK1 antagonist in the mouse and the rat. Results obtained with (+/-)-CP-96,345 confirm the lower potency of this compound in these two species when compared with reported data obtained in the guinea-pig or man.
Antinociceptive activity of NK1 receptor antagonists: non-specific effects of racemic RP67580.[Pubmed:8306108]
Br J Pharmacol. 1993 Dec;110(4):1607-13.
1. Release of substance P in the dorsal horn is considered a primary event in the perception of pain. The profile of racemic RP67580, a non-peptide antagonist at the NK1 (substance P) receptor, was examined in a range of antinociception tests on rodents. 2. At doses up to 30 mg kg-1, s.c. racemic RP67580 exhibited antinociceptive activity in writhing and formalin paw tests in mice and gerbils. Acetic acid induced writhing and the licking response to formalin were reduced to 40-50% of the level observed in vehicle-treated animals (P < 0.05). However, this agent was not active in mouse tail flick, rat paw pressure or rat and guinea-pig formalin paw tests. 3. Like racemic RP67580, the calcium channel blockers nifedipine (30 mg kg-1, i.p.) and verapamil (10 or 20 mg kg-1, s.c.) inhibited the response to formalin by approximately 60% in gerbils (P < 0.05 compared with vehicle-treated animals). 4. Evidence for calcium channel antagonist activity of RP67580 was obtained in vitro. Racemic RP67580 inhibited calcium entry into depolarized strips of guinea-pig ileum longitudinal muscle myenteric plexus (apparent KB = 587 +/- 115 nM), inhibited [3H]-diltiazem binding to rabbit skeletal membranes (IC50 = 298 nM) and depressed high threshold calcium currents in neurones cultured from rat cortex (10% inhibition at 10 microM). 5. These findings indicate that the acute antinociceptive effects of RP67580 may not be attributable to a specific interaction with NK1 receptors and may be mediated via calcium channel blockade.
Molecular basis for the species selectivity of the neurokinin-1 receptor antagonists CP-96,345 and RP67580.[Pubmed:1281470]
J Biol Chem. 1992 Dec 25;267(36):25668-71.
Two non-peptide substance P antagonists exhibit opposite rank orders of potency for the human and rat neurokinin-1 receptors. CP-96,345 shows selectivity for the human receptor, whereas RP67580 shows selectivity for the rat receptor. Amino acid sequence comparison of the two receptors reveals 22 divergent residues. To elucidate the molecular basis for the species selectivity of these antagonists, divergent residues in the human neurokinin-1 receptor were substituted by the rat homologs. Analysis of mutant receptors revealed that substitution of 2 residues (V116L and I290S) in the transmembrane domain of the human neurokinin-1 receptor is both necessary and sufficient to reproduce the antagonist binding affinities of the rat receptor. The nature of these substitutions and the magnitude of the changes in binding affinity suggest that residues 116 and 290 do not interact directly with the antagonist molecules. The present results support a model in which phylogenetically conserved residues interact directly with the antagonists, while phylogenetically divergent residues affect the local helical packing of the receptor. Such a change in local structure would lead to increased binding affinity for one class of antagonists and decreased affinity for another.
Pharmacological properties of a potent and selective nonpeptide substance P antagonist.[Pubmed:1719549]
Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10208-12.
We describe here the pharmacological properties of RP 67580 [(3aR,7aR)-7,7-diphenyl-2-[1-imino-2-(2-methoxyphenyl)ethyl] perhydroisoindol-4-one], a nonpeptide antagonist of substance P (SP). In vitro, the compound was found to inhibit in a competitive manner (Ki = 4.16 +/- 0.59 nM) [3H]SP binding to neurokinin receptors type 1 (NK1 receptors) in rat brain membranes. Contractions induced by SP and septide (a selective NK1 agonist) in guinea pig ileum were competitively inhibited by RP 67580 (pA2 = 7.16 and 7.59, respectively). Moreover, RP 67580 displayed the profile of a specific antagonist of NK1 receptors: it was not active on NK2 and NK3 receptors as seen in binding assays and in isolated preparations of rabbit pulmonary artery and rat portal vein. In the rat, low intravenous doses of RP 67580 totally inhibited the plasma extravasation induced by SP in the urinary bladder (ED50 = 0.04 mg/kg i.v.) and by antidromic electrical stimulation of the saphenous nerve in the hind paw skin (ED50 = 0.15 mg/kg i.v.). This compound was also active in two classical analgesic tests in mice: phenylbenzoquinone-induced writhing (ED50 = 0.07 mg/kg s.c.) and the formalin test (ED50 = 3.7 mg/kg s.c.). Its potency was of the same order as that of morphine. Thus we conclude that RP 67580, a SP antagonist, belongs to a class of drugs that may be useful in the management of various clinical pathologies where pain and neurogenic inflammation are involved.