Disease relevance of 1-[(3S)-3-(3,4-dichlorophenyl)-3-[2-(4-phenyl-1-azoniabicyclo[2.2.2]oct-1-yl)ethyl]-1-piperidyl]-2-(3-isopropoxyphenyl)ethanone

• SLIGRL-NH2-induced hyperalgesia was inhibited by a NK1 receptor antagonist (SR 140333) but not by indomethacin [1].
• The effects of a novel nonpeptide NK1 tachykinin receptor antagonist, SR 140333, on the functional consequences of NK1 receptor activation in a human astrocytoma cell line, U373MG, were investigated [2].
• These results therefore show that NK1 plays a major role in the development of cutaneous anaphylaxis and that SR 140333 may be an effective prophylactic drug [3].

Psychiatry related information on 1-[(3S)-3-(3,4-dichlorophenyl)-3-[2-(4-phenyl-1-azoniabicyclo[2.2.2]oct-1-yl)ethyl]-1-piperidyl]-2-(3-isopropoxyphenyl)ethanone

• Administration of [Sar9,Met(O2)11]substance P induced increased locomotor activity, as well as face washing, grooming and wet-dog shake behaviours, all of which were inhibited by the neurokinin-1 receptor antagonist, SR 140333, indicating the involvement of neurokinin-1 receptors [4].

High impact information on 1-[(3S)-3-(3,4-dichlorophenyl)-3-[2-(4-phenyl-1-azoniabicyclo[2.2.2]oct-1-yl)ethyl]-1-piperidyl]-2-(3-isopropoxyphenyl)ethanone

• At 6 weeks of age, either vehicle or a NK-1 receptor antagonist, SR 140333, was injected into the nucleus tractus solitarius of the conscious guinea pigs who were then exposed to citric acid aerosol [5].
• A selective neurokinin (NK)-1 receptor antagonist (SR 140333) reduced the neutrophil count, both with and without phosphoramidon pretreatment [6].
• Pretreatment with the bradykinin B2 receptor antagonist Hoe 140 or with the tachykinin NK1 receptor antagonist SR 140333 inhibited captopril-evoked increase in plasma extravasation [7].
• Doxantrazole (5 mg/kg intraperitoneally (i.p.)), a mast cell stabilizer, and SR 140333 (1 mg/kg i.p.) and MEN 11420 (0.1 mg/kg intravenously), respectively NK1 and NK2 receptor antagonists, were administered before GD [8].
• Enhancement of [3H]taurine release by [Sar9,Met(O2)11]-substance P (EC50 = 7.4 x 10(-9) M) was also inhibited by SR 140333 with an IC50 of 1.8 x 10(-9) M [2].

Biological context of 1-[(3S)-3-(3,4-dichlorophenyl)-3-[2-(4-phenyl-1-azoniabicyclo[2.2.2]oct-1-yl)ethyl]-1-piperidyl]-2-(3-isopropoxyphenyl)ethanone

• Stimulation-induced vasodilatation was tested after applying SR 140333 (0.1 mg/kg) and CGRP8-37 (0.3 mg/kg) alone or in combination [9].
• Intracellular recording from lumbar motoneurons of the neonatal rat spinal cord in vitro was used to study how recently developed non-peptide antagonists such as SR-140333 and SR-48698, known to block distinct subtypes of tachykinin receptors peripherally, might affect synaptic transmission elicited by electrical stimulation of dorsal root fibres [10].
• Failure of i.c.v. injected SR 140333 to increase AngII-induced drinking, as well as water intake in sated or deprived rats suggests that brain NK-1 receptor mechanisms apparently do not exert a tonic control on AngII-induced drinking and, in general, on water intake in rats [11].
• Moreover, a pre-treatment with SR 48968, a tachykinin NK2 receptor antagonist, or SR 140333, a NK1 receptor antagonist, significantly inhibited the bronchoconstriction induced by intraoesophageal HCl infusion in terms of R(L) and C(dyn)changes [12].

Anatomical context of 1-[(3S)-3-(3,4-dichlorophenyl)-3-[2-(4-phenyl-1-azoniabicyclo[2.2.2]oct-1-yl)ethyl]-1-piperidyl]-2-(3-isopropoxyphenyl)ethanone

• SR 140333, a novel, selective, and potent nonpeptide antagonist of the NK1 tachykinin receptor: characterization on the U373MG cell line [2].
• Relaxations to SLIGRL in the trachea and aorta were unaffected by the NK(1)R antagonist nolpitantium (SR 140333) but were abolished by trypsin desensitization [13].
• Effect of the tachykinin NK1 receptor antagonists, RP 67580 and SR 140333, on electrically-evoked substance P release from rat spinal cord [14].
• Effects of SR 140333 and SR 48968 on antigen and substance P-induced activation of guinea-pig alveolar macrophages [15].
• Bronchoalveolar lavage studies performed after the LAR indicated that SR 140333 caused significant inhibition of allergen-induced infiltration of eosinophils, neutrophils and lymphocytes, while SR 48968 attenuated the infiltration of neutrophils and lymphocytes, but not of eosinophils [16].

Associations of 1-[(3S)-3-(3,4-dichlorophenyl)-3-[2-(4-phenyl-1-azoniabicyclo[2.2.2]oct-1-yl)ethyl]-1-piperidyl]-2-(3-isopropoxyphenyl)ethanone with other chemical compounds

• The response to septide was prevented by intraperitoneal administration of the nonpeptide NK1 antagonist SR 140333 (1-3 mg/kg) but not by the nonpeptide NK2 receptor antagonist SR 48968, indicating that the effect was mediated specifically by NK1 receptors [17].
• Relaxations of the guinea pig trachea elicited by antidromic stimulation of capsaicin-sensitive vagal afferent nerves were markedly inhibited by 0.3 microM SR 142801 and were abolished by a combination of SR 142801 and either of the NK1-selective receptor antagonists SR 140333 and CP 99994 (0.3 microM each) [18].
• NK1 receptors played a secretory role as receptor agonists stimulated secretion and SR-140333 antagonized the response to SP response (pK(b) = 9.2) [19].
• The effect of intra-arterial NKA could not be blocked by the NK1 receptor selective antagonist SR 140,333 or the NK2 receptor selective antagonist SR 48,968, but by their combination [20].
• The tachykinin NK1 receptor antagonist, SR 140333 ((S)1-[2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)pi peridin-3-yl]ethyl]-4-phenyl-1-azoniabicyclo[2.2.2.]octane, chloride), not only inhibited mustard oil-induced plasma extravasation but also blocked the enhancement by phosphoramidon of the response to mustard oil [21].

Gene context of 1-[(3S)-3-(3,4-dichlorophenyl)-3-[2-(4-phenyl-1-azoniabicyclo[2.2.2]oct-1-yl)ethyl]-1-piperidyl]-2-(3-isopropoxyphenyl)ethanone

• All these data indicated that SR 140333 blocked SP-induced cytokine production in U373MG astrocytic cells via a specific NK1 receptor-mediated process [22].
• SR 140333 was also effective in preventing NKA- and NKB-induced oedema [23].
• RP 67580 (ED50: 0.34 mg/kg, i.v.) and SR 140333 (ED50: 0.19 mg/kg, i.v.), the non-peptide NK1 receptor antagonists, inhibited SP-induced oedema [23].
• We tested the hypothesis by determining, in conscious SHRs, whether NTS microinjections of the NK-1 receptor antagonist SR-140333 before exercise attenuated PEH [24].
• 3. The inhibitory effect of NKA (1.26 nmol min-1 kg-1) on the acid-induced gastric mucosal vasodilatation was prevented by the tachykinin NK2 receptor antagonists, MEN 10,627 (200 nmol kg-1) but left unaltered by the NK1 receptor antagonist, SR 140,333 (300 nmol kg-1) and the mast-cell stabilizer, ketotifen (4.6 mumol kg-1) [25].

Analytical, diagnostic and therapeutic context of 1-[(3S)-3-(3,4-dichlorophenyl)-3-[2-(4-phenyl-1-azoniabicyclo[2.2.2]oct-1-yl)ethyl]-1-piperidyl]-2-(3-isopropoxyphenyl)ethanone

• The potent neurokinin receptor 1 (NK1) antagonist SR-140333 has previously been shown to reduce castor oil-induced secretion in animal models [19].
• Furthermore, SR 140333 significantly (p < 0.001) suppressed ear oedema in response to intradermal injection of substance P (SP) (100 pmol/site) by i.v. administration (0.1 mg/kg,) and co-injection (50 pmol/site) [26].

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