Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacological profile of the novel tachykinin NK3 receptor antagonist SR 142801, ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl) propyl)-4-phenylpiperidin-4-yl)-N-methylacetamide), was studied at tachykinin NK1, NK2 and NK3 receptors, in several in vitro bioassays. In the guinea-pig isolated ileum longitudinal muscle preparation, SR 142801 (10 nM-1 microM) caused an insurmountable antagonism of tachykinin NK3 receptor-mediated contractions produced by senktide (apparent pKB = 9.27). The blockade induced by SR 142801 was essentially irreversible, since it was not removed by washout (up to 2 h) and was increased by prolonging the incubation from 15 to 120 min. SR 142801 showed similar antagonist potency at rat tachykinin NK3 receptors (portal vein) and rabbit tachykinin NK2 receptors (pulmonary artery) (pKB = 7.49 and 7.66, respectively), whereas it was distinctly less potent at hamster tachykinin NK2 receptors (trachea; pKB = 6.84) and inactive at guinea-pig tachykinin NK1 receptors (ileum, longitudinal muscle). In the guinea-pig whole ileum SR 142801 (100 nM) did not affect the contraction produced by capsaicin (1 microM). The combined SR 142801 pretreatment and tachyphylaxis of neuronal CGRP (calcitonin gene-related peptide) receptors produced a slight (about 25%), but significant reduction of the response to capsaicin, suggesting that tachykinin NK3 receptors play a minor role in capsaicin-induced neuronal excitation of afferent nerves in the guinea-pig ileum.
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PMID:Activity of SR 142801 at peripheral tachykinin receptors. 754 22

1. The cardiovascular responses to intravenous (i.v.) injection of natural tachykinins, substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and selective tachykinin (NK) receptor agonists, [Sar9, Met(O2)11]SP, [beta Ala8]NKA(4-10), [MePhe7]NKB and senktide were assessed in conscious, freely moving, guinea-pigs. 2. SP and [Sar9, Met(O2)11]SP (1-1000 pmol kg-1) induced dose-dependent decreases in mean arterial blood pressure (MAP) accompanied by increases in heart rate (HR). NKA evoked only weak hypotensive effects at high doses (3000 pmol kg-1) whereas [beta Ala8]NKA(4-10) (1-3000 pmol kg-1) had no effects. By contrast, NKB [MePhe7]NKB (1-10,000 pmol kg-1) and senktide (1-1000 pmol kg-1), produced dose-related hypertensive effects with the following rank order of potency: senktide > [MePhe7]NKB > NKB. Bradycardia occurred simultaneously with the increases in arterial pressure. 3. The pressor response to intravenous injection of senktide (300 pmol kg-1) was partially reduced by pretreatment with prazosin (0.71 mumol kg-1), or clonidine (0.38 mumol kg-1) and was completely inhibited by the combination of the two compounds. Atropine (1.5 mumol kg-1) suppressed the decrease in HR induced by senktide without altering the blood pressure response. These findings suggest that the blood pressure response to senktide is an indirect effect mediated by noradrenaline released from sympathetic nerve endings, whereas the bradycardia is of vagal reflex origin. 4. SR 142801, ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl) propyl)-4-phenyl-piperidin-4-yl)-N-methylacetamide), a potent and specific non-peptide NK3 receptor antagonist dose-dependently (0.46-4.6 mumol kg-1, i.v.; 4.6-46 mumol kg-1, p.o.) inhibited the cardiovascular effects of senktide and displayed a long-lasting inhibitory effect after oral administration. By contrast, SR 142806 (4.6 mumol kg-1, i.v.), the (R)-enantiomer of SR 142801 had no effect on the responses to senktide. SR 142801 at a high dose (15 mumol kg-1, i.v.) was inactive toward the [Sar9, Met(O2)11]SP-induced hypotension. 5. SR 142801 did not modify MAP in conscious guinea-pigs both after i.v. (4.6 and 15 mumol kg-1) and oral (46 and 150 mumol kg-1) administration, showing a lack of agonistic properties. However, a slight reduction in HR was observed only after i.v. injection. 6. In conclusion, these results show evident differences in the functional role of tachykinin receptors in the peripheral control of the cardiovascular system. Furthermore, a clear pressor effect of senktide, which was selectively blocked by SR 142801, was observed in conscious guinea-pigs. Hence, this antagonist appears suitable for investigating the functional role of NK3 receptors.
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PMID:Study of SR 142801, a new potent non-peptide NK3 receptor antagonist on cardiovascular responses in conscious guinea-pig. 881 31

Binding studies indicated that tachykinin NK3 binding sites in peripheral (ileum) and central (cerebral cortex) tissues of the guinea pig exhibit similar pharmacological properties. They also confirmed that the tachykinin NK3 receptor antagonist (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl) propyl)-4-phenylpiperidin-4-yl)-N-methylacetamide (SR 142801) has a higher affinity for tachykinin NK3 binding sites in the guinea pig than in the rat. SR 142801 exhibited a much lower affinity for tachykinin NK2 and NK1 binding sites. SR 142801 was shown to be a potent uncompetitive antagonist of the senktide-induced formation of [3H]inositol monophosphate in slices from the guinea-pig ileum (apparent KB = 3.2 nM, 51% reduction of the maximal response), a functional test for tachykinin NK3 receptors. In agreement with results of binding studies, the effect of SR 142801 was stereoselective since its enantiomer SR 142806 was much less potent. In the rat urinary bladder, a tissue devoid of tachykinin NK3 receptors, SR 142801 was without effect on the [Pro9]substance P- or the septide-induced formation of [3H]inositol monophosphate but it slightly reduced the response of the tachykinin NK2 receptor agonist [Lys5,MeLeu9,Nle10]neurokinin A-(4-10) (KB = 339 nM). Altogether, these data indicate that SR 142801 is a highly selective tachykinin NK3 receptor antagonist which is more potent in the guinea pig than in the rat.
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PMID:Potency and selectivity of the tachykinin NK3 receptor antagonist SR 142801. 904 6

We examined the mechanism of the inflammatory response induced by topical application of mustard oil (0.5-20.0%/20 microliters per ear) to the mouse ear compared to that of the response to capsaicin. The dose-dependent increases in plasma extravasation and ear thickness reached a maximum at approximately 30 min after mustard oil application. Topical pretreatment of ears with capsaicin (250 micrograms/ear) diminished mustard oil-induced plasma extravasation for up to day 7 but not at day 14 after treatment. However, desensitization of the exudative response was not evoked by reapplication of mustard oil to ears. The inflammatory response to mustard oil did not differ between the ears of mast cell-deficient mice and those of the congenic normal mice. Mustard oil-induced plasma extravasation was unaffected by pretreatment with histamine H1 and 5-HT2 receptor antagonists and the capsaicin-functional inhibitor, ruthenium red, which inhibit capsaicin-induced ear oedema. The endopeptidase inhibitor, phosphoramidon, enhanced the ability of mustard oil to increase dye leakage. 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. In contrast, the tachykinin NK2 receptor antagonist, SR 48968 ((S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4,- dichlorophenyl)butyl]benzamide), and the tachykinin NK3 receptor antagonist, SR 142801 ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)pro pyl)-4- phenylpiperidin-4-yl)-N-methylacetamide), had no effect on plasma extravasation. The present results demonstrated that mustard oil induces mouse skin inflammation through a mechanism different from that for capsaicin. Mediators such as histamine and 5-HT from mast cells appear to be minor factors in the response to mustard oil. In addition, evidence supports the assumption that the tachykinin NK1 receptor is involved in this model.
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PMID:Mechanism of mustard oil-induced skin inflammation in mice. 931 40

1. Inhibition of NK3 receptor agonist-induced contraction in the rabbit isolated iris sphincter muscle was used to assess the in vitro functional activity of three 2-phenyl-4-quinolinecarboxamides, members of a novel class of potent and selective non-peptide NK3 receptor antagonists. In addition, an in vivo correlate of this in vitro response, namely NK3 receptor agonist-induced miosis in conscious rabbits, was characterized with some of these antagonists. 2. In vitro senktide (succinyl-[Asp9,MePhe8]-substance P (6-11) and [MePhe7]-neurokinin B ([MePhe7]-NKB) were potent contractile agents in the rabbit iris sphincter muscle but exhibited quite different profiles. Senktide produced monophasic log concentration-effect curves with a mean pD2=9.03+/-0.06 and mean nH=1.2+/-0.02 (n=14). In contrast, [MePhe7]-NKB produced shallow log concentration-effect curves which often appeared biphasic (nH=0.54+/-0.04, n=8), preventing the accurate determination of pD2 values. 3. The contractile responses to the NK3 receptor agonist senktide were antagonized in a surmountable and concentration-dependent manner by SB 223412 ((-)-(S)-N-(alpha-ethylbenzyl)-3-hydroxy-2-phenylquinoline-4-ca rboxamide; 3-30 nM, pA2=8.4, slope=1.8+/-0.3, n=4). SB 222200 ((-)-(S)-N-(alpha-ethylbenzyl)-3-methyl-2-phenylquinoline-4-car box amide; 30-300 nM, pA2=7.9, slope=1.4+/-0.06, n=4) and SB 218795 ((-)-(R)-N-(alpha-methoxycarbonylbenzyl)-2-phenylquinoline-4-carboxamide; 0.3 and 3 microM apparent pKB=7.4+/-0.06, n=6). 4. Contractile responses to the NK3 receptor agonist [MePhe7]-NKB in the rabbit iris sphincter muscle were unaffected by SB 218795 (0.3 and 3 microM, n=8). In contrast, SB 223412 (30 and 300 microM n=4) and SB 222200 (0.3 and 3 microM, n=4) inhibited responses to low concentrations (< or = 1 nM), to a greater extent than higher concentrations (> 1 nM) of [MePhe7]-NKB. Furthermore, log concentration-effect curves to [MePhe7]-NKB became steeper and monophasic in the presence of each antagonist. 5. SB 218795 (3 microM, n=4) had no effect on contractions induced by transmural nerve stimulation (2 Hz) or substance P, exemplifying the selectivity of this class of antagonist for functional NK3 receptors over NK1 receptors in the rabbit. 6. In vivo, senktide (1, 10 and 25 microg i.v., i.e. 1.2, 11.9 and 29.7 nmol, respectively) induced concentration-dependent bilateral miosis in conscious rabbits (maximum pupillary constriction=4.25+/-0.25 mm; basal pupillary diameter 7.75+/-0.48 mm; n=4). The onset of miosis was within 2-5 min of application of senktide and responses lasted up to 30 min. Responses to two i.v. administrations of 25 microg senktide given 30 min apart revealed no evidence of tachyphylaxis. Topical administration of atropine (1%) to the eye enhanced pupillary responses to 25 microg senktide. This was probably due to the mydriatic effect of atropine since it significantly increased baseline pupillary diameter from 7.0+/-0.4 mm to 9.0+/-0.7 mm (n=4), thereby increasing the maximum capacity for miosis. Senktide-induced miosis was inhibited by SB 222200 (1 and 2 mg kg[-1], i.v., i.e. 2.63 and 5.26 micromol kg[-1]; maximum inhibition 100%; n=3-4), SB 223412 (0.5 and 1 mg kg[-1], i.v., i.e. 1.31 and 2.61 micromol kg[-1]; maximum inhibition 100%; n=3), SB 218795 (0.5 and 1 mg kg[-1] i.v., i.e. 1.26 and 2.52 micromol kg-1; maximum inhibition 78%; n=3), and the structurally distinct NK3 receptor antagonist SR 142801 ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)propyl)-4-phenylepipiperidin-4-yl)-N-methylacetamide; 1.5mg kg-1, i.v., i.e. 2.47micromol kg-1, maximum inhibition 92%; n=3). 7. Topical administration of senktide (25microg; 29.7nmol) to the eye induced unilateral miosis in the treated eye only. At this dose there was no significant difference (P<0.05) between pupillary constriction obtained by topical or i.v. senktide, and topically administered atropine had no significant effect on responses to topical senktide (n=4). 8. [MePhe7]-NKB (125, 250 and 500microg, i.v., i.e. 98.31, 196.62 and 393.24nmol, respectively) also induced bilateral miosis in conscious rabbits (maximum pupillary constriction=4.13+/-0.30mm; n=4), but in contrast to in vitro studies this agonist was approximately 100 fold less potent than senktide. [MePhe7]-NKB-induced miosis was inhibited by SB 222200 (5mg kg-1, i.v., i.e. 13.14micromol kg-1; maximum inhibition 69%; n=3). 9. In summary, SB 223412, SB 222200 and SB 218795 are potent and selective antagonists of NK3 receptor-mediated contraction in the rabbit isolated iris sphincter muscle. In addition, NK3 receptor agonist-induced miosis in conscious rabbits is a good in vivo correlate of the in vitro rabbit iris sphincter muscle preparation and appears to be a useful model for characterizing the pharmacodynamic profile and efficacy of structurally distinct NK3 receptor antagonists, such as SB 222200, SB 223412, SB 218795 and SR 142801.
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PMID:In vitro and in vivo characterization of NK3 receptors in the rabbit eye by use of selective non-peptide NK3 receptor antagonists. 935 3

1. In the conscious rat, three tachykinin NK3 receptor antagonists, namely SR142801 ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)pro pyl)-4-phenylpiperidin-4-yl)-N-methylacetamide), R820 (3-indolylcarbonyl-Hyp-Phg-N(Me)-Bzl) and R486 (H-Asp-Ser-Phe-Trp-beta-Ala-Leu-Met-NH2) were assessed against the intracerebroventricular (i.c.v.) effects induced by senktide, a selective NK3 receptor agonist, on mean arterial blood pressure (MAP), heart rate (HR) and motor behaviour. 2. Senktide (10-650 pmol per animal; i.c.v; n = 4-16) at the lowest dose caused a significant fall in MAP (-10 +/- 6 mmHg), while at the highest doses (100 and 650 pmol), senktide caused a rise in MAP (9 +/- 3 and 12 +/- 1 mmHg, respectively) when compared to vehicle. The intermediate doses (25 and 65 pmol) had no effect on MAP. The highest two doses caused a tachycardia of 62 +/- 15 and 88 +/- 8 beats min(-1), respectively. The dose of 65 pmol had a biphasic effect on HR, an initial bradycardia of 47 +/- 12 beats min(-1) followed by a tachycardia of 46 +/- 14 beats min(-1). The lowest doses caused either a rise of 52 +/- 10 beats min(-1) (25 pmol) or no effect (10 pmol) on HR. All doses of senktide caused similar increases in face washing, sniffing and wet dog shakes except at the dose of 100 pmol, when wet dog shakes were more than double those observed with the other doses. 3. The antagonist SR142801 (100 pmol -65 nmol per animal; i.c.v.; n = 6-8) caused increases in MAP at the highest two doses (6.5 and 65 nmol) while HR, dose-dependently, increased (23 +/- 6 to 118 +/- 26 beats min[-1]) and the onset dose-dependently decreased. The (R)-enantiomer, SR142806 (100 pmol - 65 nmol per animal; i.c.v.; n = 6-8) only caused rises in MAP (13 +/- 2 mmHg) and HR (69 +/- 11 beats min[-1]) at the highest dose. These drugs had no apparent effect on behaviour, except for the highest dose of SR142801 which increased sniffing. The antagonist R820 (650 pmol - 6.5 nmol per animal; i.c.v.; n = 6) had no effect on MAP or HR and only increased sniffing behaviour at 6.5 nmol. At 650 pmol (n = 6), R486 had no effect on any variable, but at 3.25 nmol, i.c.v. (n = 4) a delayed tachycardia and a significant increase in all behavioural variables were observed. 4. The cardiovascular responses induced by 6.5 nmol SR142801 and 25 pmol senktide were inhibited by R820 (6.5 nmol, 5 min earlier i.c.v.). In contrast, R820 failed to affect the central cardiovascular and behavioural responses induced by 10 pmol [Sar9, Met(O2)11]substance P, a NK1 receptor selective agonist. The senktide-induced behavioural changes were not inhibited by R820 (6.5 nmol, i.c.v.) while R486 (650 pmol, i.c.v.) blocked both the cardiovascular and behavioural responses to 25 pmol senktide. A mixture of antagonists for NK1 (RP67580; 6.5 nmol) and NK2 (SR48968; 6.5 nmol) receptors injected i.c.v. did not affect the cardiovascular response to SR142801. Cross-desensitization was shown between the central responses to SR142801 and senktide, but not between SR142801 and [Sar9, Met(O2)11]substance P. 5. The antagonists SR142801 and SR142806 (6.5-650 nmol kg(-1); n = 5-7), given i.v., did not evoke any cardiovascular or behavioural changes, except a delayed bradycardia for SR142806 (650 nmol kg[-1]), and also failed to inhibit the increase in MAP evoked by senktide (4 nmol kg(-1), i.v.). However, at the highest dose, both drugs slightly reduced the senktide-induced tachycardia. 6. Although the present data are consistent with the in vitro pharmacological bioassays and binding data, showing that SR142801 is a poor antagonist at rat peripheral NK3 receptors, they suggest that SR142801 has a partial agonist action at these receptors centrally. A separation of the cardiovascular and behavioural effects mediated by central NK3 receptor activation was achieved with SR142801 and R820 but not with R486. These results could be explained by the existence of NK3 receptor subtypes in the rat or by the differential activation and inhibition of the same receptor protein linked to the production of different second messengers. Differences in the pharmacokinetic or pharmacodynamic properties of the antagonists cannot be excluded at this time.
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PMID:Cardiovascular and behavioural effects of intracerebroventricularly administered tachykinin NK3 receptor antagonists in the conscious rat. 937 60

Distension of the rat intestine causes a cardiovascular response which is indicative of nociception. Since tachykinins are involved in nociception, we tested the effect of neurokinin receptor antagonists against the distension-induced response. The jejunal distension-induced depressor responses were inhibited in a dose-dependent fashion by CP 99,994 (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine, tachykinin NK1 receptor antagonist, ED50 = 0.8 mg/kg) and SR 48968 (S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichloropheny l)butyl]benzamide, tachykinin NK2 receptor antagonist, ED50 = 0.7 mg/kg). SR 142801 (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)prop yl)-4-phenylpiperidin-4-yl)-N-methylacetamide, tachykinin NK3 receptor antagonist, 0.3-10 mg/kg) did not significantly affect the depressor responses to jejunal distension. In addition, CP 99,994 (3 mg/kg) and SR 48968 (3 and 10 mg/kg) reduced sensitivity to distension as revealed by a 2.7-fold (CP 99.994, 3 mg/kg), 2.6-fold (SR 48968, 3 mg/kg) and 4.7-fold (SR 48968, 10 mg/kg) increase in the threshold pressure. Intestinal compliance was not affected by the antagonists. In conclusion, these results suggest that tachykinin NK1 and NK2 but not NK3 receptors are possibly involved in the rat jejunal distension pain response.
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PMID:Effects of tachykinin receptor antagonists on the rat jejunal distension pain response. 959 22

We examined tachykinin-induced contractions of uteri from rats during the oestrous cycle. The potencies of substance P, neurokinin A, neurokinin B and the tachykinin NK2 receptor-selective agonist, [Lys5, MeLeu9, Nle10] neurokinin A-(4-10), and of the non-peptide tachykinin NK1, NK2 and NK3 receptor antagonists (S)1-[2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)pip eridin-3-yl]ethyl]-4phenyl-1-azonia-bicyclo[2.2.2]octane (SR 140333), (S)-N-methyl-N [4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butyl]benzam ide (SR 48968) and (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)prop yl)-4-phenylpiperidin-4-yl)-N-methylacetamide (SR 142801), were examined. The relative agonist potencies, i.e., [Lys5, MeLeu9, Nle10] neurokinin A-(4-10) > or = neurokinin A > neurokinin B > or = substance P were similar in preparations from rats in dioestrus/metoestrus and those in proestrus/oestrus. Apparent pK(B) values for SR 48968 versus neurokinin A and [Lys5, MeLeu9, Nle10] neurokinin A-(4-10), were 9.9 and 9.2, respectively, indicating activation of an NK2 receptor. SR 140333 (10 nM) produced only a small rightward shift of the log concentration-response curve to substance P. SR 48968 (3 nM), but not SR 142801 (100-300 nM) reduced the effect of neurokinin B. These data indicate that in the rat tachykinin-induced contractions of the uteri during the oestrous cycle are mediated primarily by tachykinin NK2 receptors, and that fluctuations in ovarian hormonal levels during the oestrous cycle have little influence on the uterine response to tachykinins.
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PMID:NK2 receptors mediate tachykinin-induced contractions of rat uterus during the oestrous cycle. 1044 89

The receptor types mediating sensory neuropeptide-induced coronary vasodilatation were elucidated on isolated guinea pig hearts perfused with isotonic buffer containing 20 mM KCl. Substance P and the selective neurokinin-1 (NK1) receptor agonist [Sar9, Met(O2)11]-substance P produced dose-dependent reductions in perfusion pressure, but the selective NK2 receptor agonist [Nle10]-neurokinin A4-10 and the selective NK3 receptor agonist [MePhe7]-neurokinin B produced no change. The vasorelaxant effects of substance P and the NK1 receptor agonist were abolished by the selective NK1 receptor antagonist FK888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-L-prolyl]-N-methy l-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide), whereas the selective NK2 receptor antagonist SR48968 ((S)-N-methyl-N-[4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl )-butyl] benzamide) and the selective NK3 receptor antagonist SR142801 ((S)-(N)-( 1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)propyl)4-p henylpiperidin-4-yl)-N-methylacetamide) produced partial inhibition on their responses. Calcitonin gene-related peptide (CGRP) produced dose-dependent vasodilatation on the guinea pig coronary blood vessels, which was significantly (p = 0.0067) inhibited by the selective CGRP1 receptor antagonist hCGRP8-37. The selective CGRP2 receptor agonist [Cys(acetomethoxy)2,7]CGRP had no effect on perfusion pressure. These results demonstrate that the sensory neuropeptides substance P and CGRP are effective vasodilators of the guinea pig coronary vascular bed. The receptor types mediating their vasorelaxant effects were identified to be the NK1 receptors and CGRP1 receptors, respectively.
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PMID:Pharmacologic characterization of receptor types mediating coronary vasodilator actions of sensory neuropeptides in the guinea pig. 1077 97

Several observations suggest that tachykinins (substance P, neurokinin A and neurokinin B) are involved in the pathogenesis of pulmonary diseases and elicit several airway responses such as bronchoconstriction and neurogenic inflammation via interactions with specific receptors denoted NK(1), NK(2) and NK(3). We have investigated the effect of a selective antagonist for tachykinin NK(3) receptor, SR 142801 ((R)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)propyl)-4-phenylpiperidin-4-yl-N-methylacetamide), on the inflammatory cell recruitment in ovalbumin-sensitized and -challenged mice used as a model of allergic asthma. Twenty hours after the two-ovalbumin challenges, differential cell counts were calculated and indicated that SR 142801 caused a significant decrease in the number of neutrophils and eosinophils. Forty hours after the last ovalbumin exposure, SR 142801 induced a significant decrease in the recruitment of eosinophils. These results suggest that tachykinins and tachykinin NK(3) receptors can interfere with cell recruitment in inflammatory response.
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PMID:Inhibition of inflammatory cell recruitment by the tachykinin NK(3)-receptor antagonist, SR 142801, in a murine model of asthma. 1151 37


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