Nuvenzepine
(Synonyms: 奴文西平) 目录号 : GC32667
Nuvenzepine是mAChR的拮抗剂，之前在临床一期试验中用来治疗胃痉挛。
Cas No.:96487-37-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Nuvenzepine is an mAChR antagonist previously in phase I clinical trials for the treatment of gastrospasm.
Nuvenzepine shows a four-fold higher affinity than pirenzepine in competitively antagonizing acetylcholine-induced contractions on isolated ileal musculature and on longitudinal ileum dispersed cells. Nuvenzepine is almost equipotent to pirenzepine in competitively preventing bethanechol-induced gall-bladder contractions and it displays a four-fold higher potency than pirenzepine in blocking vagal-stimulated tracheal constrictions[1].
Intraduodenally administration of Nuvenzepine displays a long-lasting and dose-dependent inhibition of neostigmine-induced intestinal motility in anaesthetized cats. On ileal motor activity, Nuvenzepine shows a potency 10 times greater than that of pirenzepine. Nuvenzepine is also active, unlike pirenzepine, on colonic stimulated motility. Furthermore, in conscious cats, Nuvenzepine inhibits pentagastrin-stimulated gastric acid secretion resulting 25-30 times more potent than pirenzepine[2]. Nuvenzepine has been found to be very active in inhibiting gastric acid secretion and intestinal hypermotility in rats, with very slight atropine-like side effects. The oral absorption rate is relatively slow, that the absolute bioavailability is 30 to 40%, that the elimination rate is slow and there is no accumulation in the body, and that there is very little metabolism[3].
[1]. Barocelli E, et al. Functional comparison between nuvenzepine and pirenzepine on different guinea pig isolated smooth muscle preparations. Pharmacol Res. 1994 Aug-Sep;30(2):161-70. [2]. Barocelli E, et al. Gastrointestinal activities of a new pirenzepine-analog, nuvenzepine, in the cat. Farmaco. 1990 Oct;45(10):1089-99. [3]. Caselli G, et al. Determination of nuvenzepine in human plasma by a sensitive [3H]pirenzepine radioreceptor binding assay. J Pharm Sci. 1991 Feb;80(2):173-7.
| Cas No. | 96487-37-5 | SDF | |
| 别名 | 奴文西平 | ||
| Canonical SMILES | O=C1C2=CC=CN=C2N(C(C3CCN(C)CC3)=O)C4=CC=CC=C4N1 | ||
| 分子式 | C19H20N4O2 | 分子量 | 336.39 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -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 | 2.9727 mL | 14.8637 mL | 29.7274 mL |
| 5 mM | 0.5945 mL | 2.9727 mL | 5.9455 mL |
| 10 mM | 0.2973 mL | 1.4864 mL | 2.9727 mL |
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Functional comparison between Nuvenzepine and pirenzepine on different guinea pig isolated smooth muscle preparations
Pharmacol Res 1994 Aug-Sep;30(2):161-70.PMID:7816744DOI:10.1016/1043-6618(94)80007-3.
The antimuscarinic agents Nuvenzepine and pirenzepine were tested on four guinea pig isolated smooth muscle preparations in order to better investigate the existence of differences in the functional activities of such antagonists, as suggested by previous reports. The effects of both compounds were compared to those of atropine. Nuvenzepine showed a four-fold higher affinity than pirenzepine in competitively antagonizing acetylcholine-induced contractions on isolated ileal musculature (pA2 = 7.08 +/- 0.15) and on longitudinal ileum dispersed cells (pA2 = 7.11 +/- 0.19). By contrast, unlike pirenzepine which was ineffective, Nuvenzepine inhibited histamine-induced ileal motor activity in a dualistic manner, behaving as an irreversible competitive H1 antagonist (pA2 = 5.02 +/- 0.11). Nuvenzepine was almost equipotent to pirenzepine in competitively preventing bethanechol-induced gall-bladder contractions (pA2 = 7.23 +/- 0.16) and it displayed a four-fold higher potency than pirenzepine in blocking vagal-stimulated tracheal constrictions (pIC50 = 6.77 +/- 0.06). Both compounds were definitely less potent than atropine. On the whole, these findings indicate that, on the selected preparations, Nuvenzepine substantially shares the antimuscarinic properties of pirenzepine but it is also endowed with a (weak) H1-blocking action. Furthermore, based on some observations, the presence in gallbladder smooth muscle of muscarinic receptors distinguishable from those of ileum could be speculated.
Gastrointestinal activities of a new pirenzepine-analog, Nuvenzepine, in the cat
Farmaco 1990 Oct;45(10):1089-99.PMID:2095154doi
Nuvenzepine, a new pirenzepine-analog, administered intraduodenally, displayed a long-lasting and dose-dependent inhibition of neostigmine-induced intestinal motility in anaesthetized cats. On ileal motor activity, the compound showed a potency 10 times greater than that of pirenzepine, and, although to a lesser extent, it was also active, unlike pirenzepine, on colonic stimulated motility. Furthermore, in conscious cats, Nuvenzepine inhibited pentagastrin-stimulated gastric acid secretion resulting 25-30 times more potent than pirenzepine. The observed differences between antisecretory and antispastic activities displayed by Nuvenzepine and pirenzepine suggest that the new pirenzepine-analog may act on gastrointestinal functions through an additional non-anticholinergic mechanism.
Determination of Nuvenzepine in human plasma by a sensitive [3H]pirenzepine radioreceptor binding assay
J Pharm Sci 1991 Feb;80(2):173-7.PMID:2051325DOI:10.1002/jps.2600800219.
A sensitive method for the quantitation of small amounts of Nuvenzepine, a new M1-selective antimuscarinic drug, in plasma is described. The analytical method involves the use of a radioreceptor binding assay based on [3H]pirenzepine displacement in rat cerebral cortex homogenates; no previous extraction is required. The method is reliable, with an interassay CV ranging from 5 to 10%, and allows the analysis of greater than 100 samples/experiment. The limit of detection is approximately 0.1 ng/assay. Using this method we have determined the plasma levels of Nuvenzepine in eight healthy volunteers treated PO with 15 or 25 mg of Nuvenzepine.HCl. The pharmacokinetic parameters obtained were (for 15 and 25 mg): Cmax, 64 and 131 ng/mL; AUC0-infinity, 851 and 1379 ng.h/mL; t1/2, 8.6 and 7.2 h. These values are in good agreement with those obtained using an HPLC method. Therefore, this radioreceptor binding assay proved to be simple, rapid, and specific for the determination of low levels of Nuvenzepine in human plasma.
Regional differences in motor responsiveness to antimuscarinic drugs in rabbit isolated small and large intestine
Pharmacol Res 1995 Jan;31(1):43-8.PMID:7784305DOI:10.1016/1043-6618(95)80046-8.
The pirenzepine-related analogue, Nuvenzepine, and the antagonists selective for the three muscarinic receptor subtypes 4-DAMP (M1 and M3 receptors), pirenzepine (M1 receptors), methoctramine (M2 receptors) have been tested on rabbit isolated small and large intestinal regions provided with spontaneous motor activity. The employed drugs differently affected intestinal motility patterns. The ileum pendular movements as well as the proximal colon and taenia coli tone, spike amplitude and frequency were concentration-dependently inhibited by the compounds here employed. Their pIC50 values followed the rank order of potency generally reported for the involvement of the M3 muscarinic receptors (4-DAMP > or = atropine > Nuvenzepine > or = pirenzepine > methoctramine). Unlike Nuvenzepine and the other antimuscarinics assayed, the M1 selective antagonist pirenzepine, at nanomolar concentrations, was able to enhance the proximal taenia coli motility patterns suggesting that a M1-inhibitory pathway might operate in the physiological modulation of taenia coli motility. At variance with longitudinal ileum and colon contractile activity, proximal circular colon motility was resistant to muscarinic as well as to alpha 1-, H1-, 5-HT-blockade indicating that NANC neuronal mechanisms could act at this level. In summary, these data provide evidence that, at intestinal level, Nuvenzepine is almost completely devoid of reliable M1-linked effect thus possessing a different pharmacological selectivity at muscarinic receptor subtypes with respect to pirenzepine. Furthermore, it emerges that rabbit spontaneous small and large intestinal motility is probably driven by different physiological mechanisms regional-related. The peculiar circular colon refractoriness deserves further studies to be extended to the human tissue.
Quinolizidinyl derivatives of 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one as ligands for muscarinic receptors
Bioorg Med Chem Lett 1999 Oct 18;9(20):3031-4.PMID:10571170DOI:10.1016/s0960-894x(99)00528-4.
Quinolizidinyl derivatives of the tricyclic systems characterizing pirenzepine and Nuvenzepine, were prepared and tested as ligands for muscarinic M1, M2 and M3 receptors; 5,11-dihydro-11-[(S-lupinyl)-thioacetyl]-6H-pyrido[2,3-b][1, 4]benzodiazepin-6-one exhibited IC50 = 10 nM for M1 and 760 nM for both M2 and M3 subtypes. During the synthesis some interesting side compounds were isolated and characterized.