Nylidrin
(Synonyms: 脑清) 目录号 : GC48801
An agonist of β-ARs and antagonist of NR1A/2B subunit-containing NMDA receptors
Cas No.:447-41-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >85.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Nylidrin is an agonist of β-adrenergic receptors and antagonist of NR1A/2B subunit-containing NMDA receptors.1,2 It binds to β-adrenergic receptors (Kd = 0.37 µM) and activates adenylate cyclase with a Ka value of 1.3 µM.1 Nylidrin is selective for NR1A/2B over NR1A/2A and NR1A/2C subunit-containing NMDA receptors (IC50s = 0.18, 32, and 42 µM, respectively, for the recombinant receptors expressed in Xenopus oocytes).2 It inhibits NMDA-induced currents in primary rat cortical neurons (IC50 = 0.22 µM). It also decreases blood pressure and increases heart rate in spontaneously hypertensive rats (SHRs) with a minimum effective dose (MED) of 0.5 mg/kg.3 Nylidrin (20 and 100 µM) inhibits influenza hemagglutinin 2-mediated membrane fusion in Vero E6 cells.4 It inhibits infection of MDCK cells by H1N1 and H3N2 influenza isolates in vitro (EC50s = 7.2 and 12.1 µM, respectively) and prevents infection in a mouse model of mouse-adapted H1N1 infection.
1.Bilezikian, J.P., Dornfeld, A.M., and Gammon, D.E.Structure-binding-activity analysis of beta-adrenergic amines—I. Binding to the beta receptor and activation of adenylate cyclaseBiochem. Pharmacol.27(10)1445-1454(1978) 2.Whittemore, E.R., Ilyin, V.I., Konkoy, C.S., et al.Subtype-selective antagonism of NMDA receptors by nylidrinEur. J. Pharmacol.337(2-3)197-208(1997) 3.Yen, T.T., and Pearson, D.V.Nylidrin: A potent antihypertensive agent in hypertensive ratsRes. Commun. Chem. Pathol. Pharmacol.23(1)11-28(1979) 4.Jang, Y., Shin, J.S., Lee, J.-Y., et al.In vitro and in vivo antiviral activity of nylidrin by targeting the hemagglutinin 2-mediated membrane fusion of influenza A virusViruses12(5)581(2020)
| Cas No. | 447-41-6 | SDF | |
| 别名 | 脑清 | ||
| Canonical SMILES | OC1=CC=C(C(C(C)NC(CCC2=CC=CC=C2)C)O)C=C1 | ||
| 分子式 | C19H25NO2 | 分子量 | 299.4 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:7): 0.12 mg/ml | 储存条件 | -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.34 mL | 16.7001 mL | 33.4001 mL |
| 5 mM | 0.668 mL | 3.34 mL | 6.68 mL |
| 10 mM | 0.334 mL | 1.67 mL | 3.34 mL |
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Effects of isoxuprine and Nylidrin on adrenoreceptors in rat vas deferens
J Auton Pharmacol 1985 Sep;5(3):213-9.PMID:2997229DOI:10.1111/j.1474-8673.1985.tb00122.x.
The interaction of isoxuprine and Nylidrin with alpha 1- and beta 2-adrenoreceptors in rat vas deferens was examined using radioligand binding assays and physiological studies in vitro. Isoxuprine and Nylidrin have a greater affinity for binding to alpha 1 (isoxuprine KD = 59 +/- 15 nM; Nylidrin KD = 41 +/- 3 nM) than beta 2-(isoxuprine KD = 3,900 +/- 500 nM; Nylidrin KD = 900 +/- 50 nM) adrenoreceptors in rat vas deferens. Vas deferens from rats pretreated for 16-24 h with reserpine (3 mg/kg i.p.) were exposed to 10 microM phenoxybenzamine for 15 min to inactivate alpha-adrenoreceptors. Under these conditions high concentrations of both isoxuprine and Nylidrin relaxed vas deferens contracted with 55 mM K+, however the relaxation was not blocked by the beta-adrenoreceptor antagonist propranolol (10 microM). Both isoxuprine and Nylidrin were potent competitive antagonists of alpha 1-adrenoreceptor mediated contraction of vas deferens. pA2 values for isoxuprine (6.9 +/- .05) and Nylidrin (7.1 +/- .08) agreed well with KD values for binding to alpha 1-adrenoreceptors in vas deferens. The greater potency of isoxuprine and Nylidrin in inhibiting alpha 1-adrenoreceptors than binding to beta 2-adrenoreceptors or causing nonspecific relaxation suggest that alpha-adrenoreceptor antagonist actions of these drugs may be important in their ability to inhibit smooth muscle tone.
In Vitro and In Vivo Antiviral Activity of Nylidrin by Targeting the Hemagglutinin 2-Mediated Membrane Fusion of Influenza A Virus
Viruses 2020 May 25;12(5):581.PMID:32466302DOI:10.3390/v12050581.
Influenza A virus, one of the major human respiratory pathogens, is responsible for annual seasonal endemics and unpredictable periodic pandemics. Despite the clinical availability of vaccines and antivirals, the antigenic diversity and drug resistance of this virus makes it a persistent threat to public health, underlying the need for the development of novel antivirals. In a cell culture-based high-throughput screen, a β2-adrenergic receptor agonist, Nylidrin, was identified as an antiviral compound against influenza A virus. The molecule was effective against multiple isolates of subtype H1N1, but had limited activity against subtype H3N2, depending on the strain. By examining the antiviral activity of its chemical analogues, we found that ifenprodil and clenbuterol also had reliable inhibitory effects against A/H1N1 strains. Field-based pharmacophore modeling with comparisons of active and inactive compounds revealed the importance of positive and negative electrostatic patterns of phenyl aminoethanol derivatives. Time-of-addition experiments and visualization of the intracellular localization of nucleoprotein NP demonstrated that an early step of the virus life cycle was suppressed by Nylidrin. Ultimately, we discovered that Nylidrin targets hemagglutinin 2 (HA2)-mediated membrane fusion by blocking conformational change of HA at acidic pH. In a mouse model, preincubation of a mouse-adapted influenza A virus (H1N1) with Nylidrin completely blocked intranasal viral infection. The present study suggests that Nylidrin could provide a core chemical skeleton for the development of a direct-acting inhibitor of influenza A virus entry.
Subtype-selective antagonism of NMDA receptors by Nylidrin
Eur J Pharmacol 1997 Oct 22;337(2-3):197-208.PMID:9430414DOI:10.1016/s0014-2999(97)01292-2.
The 1,4-di-substituted piperidines ifenprodil, eliprodil, CP 101,606 ((1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol ) and Ro 25-6981 ((R-(R*,S*))-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenyl-methyl)-1- piperidinepropanol) are allosteric antagonists of NMDA receptors. Inhibition of diheteromeric NMDA receptors by this class of antagonist is characterized by pronounced selectivity for NR1/2B subunit combinations. In the current study, we assayed effects of Nylidrin, a structurally-related non-piperidine, on recombinant and neuronal NMDA receptors. Nylidrin was a potent (IC50 = 0.18 microM) antagonist of NR1A/2B receptors expressed in Xenopus oocytes and was at least 150-fold weaker against NR1A/2A and NR1A/2C receptors. The blockade of NR1A/2B responses by Nylidrin was not surmounted by increasing the concentrations of glutamate or glycine and was not voltage-dependent. Potency of inhibition increased approximately 3-fold upon lowering extracellular pH from 8 to 6.8. Nylidrin inhibited NMDA responses in cultured rat cortical neurons with similar potency and apparent mechanism of action as the NR1A/2B receptors. Our results suggest that Nylidrin interacts with the same allosteric inhibitory site previously described for the related piperidine antagonists, and should serve as a structural lead for designing novel subtype-selective inhibitors of NMDA receptors.
Nylidrin: a potent anti-hypertensive agent in hypertensive rats
Res Commun Chem Pathol Pharmacol 1979 Jan;23(1):11-28.PMID:441505doi
Nylidrin HCl lowered the blood pressure and increased the heart rate of conscious, spontaneously hypertensive rats (SHR), Goldblatt hypertensive rats, and DOCA hypertensive rates. In SHR, the minimum effective dose was 0.5 mg/kg, s.c. At that dose, the anti-hypertensive activity of Nylidrin lasted more than 3 hours. Propranolol reversed both effects on blood pressure and heart rate by Nylidrin, whereas atenolol, a specific cardiac beta 1 blocker, only blocked or reversed the tachycardia caused by Nylidrin but did not block the anti-hypertensive effect of the compound. In normotensive rats of Wistar/Kyoto strain (WKY) and Holtzman strain, Nylidrin at 5 or 10 mg/kg, s.c., produced a transient hypotensive effect which lasted less than an hour and tachycardia that persisted for several hours. In WKY, atenolol prolonged the hypotensive activity of the compound by partially reversing the tachycardia. These observations indicate that SHR is more sensitive than WKY to the anti-hypertensive activity of Nylidrin, which is probably caused by vasodilatation mediated by beta 2 receptors.
Ocular hypotension in the rabbit. Receptor mechanisms of pirbuterol and Nylidrin
Invest Ophthalmol Vis Sci 1985 Feb;26(2):163-9.PMID:2857689doi
Pirbuterol and Nylidrin, both purported sympathomimetic amines, reduced intraocular pressure (IOP) when given topically (50 microliter, 0.1%) to albino rabbits. Pirbuterol increased the cyclic-AMP concentration in aqueous humor by a factor of 3.25, while Nylidrin had no effect on aqueous cyclic-AMP nor on adenylate cyclase activity of iris-ciliary body membranes assayed in vitro. Studies of the receptor affinity of pirbuterol, timolol and Nylidrin were carried out on iris-ciliary body membranes by competition binding with radioactive ligands. Four ligands were used that appear to label separate subpopulations of adrenergic receptors; dihydroalprenolol (beta-receptors), WB-4101 (alpha 1-receptors) prazosin (alpha 1-receptor subpopulation) and yohimbine (alpha 2-receptors). Pirbuterol and timolol showed exclusive selectivity for beta-receptors with high affinities (Kd 12.6 and 0.48 nM, respectively) compared with other adrenergic receptor populations in iris-ciliary body. Nylidrin had high affinities for beta-receptors (Kd 22 nM) and for the subpopulation of alpha 1-receptors labelled by prazosin (Kd 6.5 nM), but showed 100-fold lower affinity and complex binding characteristics to the two other classes of alpha-adrenergic receptor sites labelled by WB-4101 and yohimbine, respectively. The results show that pirbuterol and timolol are highly beta-receptor selective and that hypotensive responses to these drugs are not mediated by the other classes of alpha-adrenergic receptor determined in this study. However, the hypotensive response to Nylidrin may be related to its prazosin-like (alpha 1-receptor) antagonist properties with additional activity at beta-receptors.