SCH 32615
目录号 : GC61457
SCH32615是一种脑啡肽酶(enkephalinase，负责内源性脑啡肽降解的酶)的抑制剂。SCH32615可以增强小鼠手术和妊娠引起的镇痛作用。
Cas No.:83861-02-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
SCH 32615 is an enkephalinase (the enzymes responsible for the degradation of endogenous enkephalins) inhibitor. SCH 32615 can enhance surgery- and pregnancy-induced analgesia in mice[1][2].
SCH 32615 blocks the degradation of Met5-enkephalin by isolated enkephalinase, with the Ki of 19.5 nM[3].
SCH 32615 (150 mg/kg; s.c.) enhances surgery activated endogenous analgesia in mice[1].
[1]. Jayaram A, et, al. An enkephalinase inhibitor, SCH 32615, augments analgesia induced by surgery in mice. Anesthesiology. 1995 May;82(5):1283-7. [2]. Jayaram A, et, al. SCH 32615, an enkephalinase inhibitor, enhances pregnancy-induced analgesia in mice. Anesth Analg. 1995 May;80(5):944-8. [3]. Chipkin RE, et, al. Pharmacology of SCH 34826, an orally active enkephalinase inhibitor analgesic. J Pharmacol Exp Ther. 1988 Jun;245(3):829-38.
| Cas No. | 83861-02-3 | SDF | |
| Canonical SMILES | OC([C@H](CC1=CC=CC=C1)N[C@H](C(NCCC(O)=O)=O)CC2=CC=CC=C2)=O | ||
| 分子式 | C21H24N2O5 | 分子量 | 384.43 |
| 溶解度 | DMSO: 125 mg/mL (325.16 mM) | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6013 mL | 13.0063 mL | 26.0125 mL |
| 5 mM | 0.5203 mL | 2.6013 mL | 5.2025 mL |
| 10 mM | 0.2601 mL | 1.3006 mL | 2.6013 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
SCH 32615, an enkephalinase inhibitor, enhances pregnancy-induced analgesia in mice
Anesth Analg 1995 May;80(5):944-8.PMID:7726437DOI:10.1097/00000539-199505000-00015.
Increased tolerance to noxious stimuli during pregnancy has been demonstrated. The purpose of this study was to examine the effect of SCH 32615, an inhibitor of one of the enzymes (enkephalinase) responsible for the degradation of endogenous enkephalins, on pregnancy-induced analgesia in mice. Analgesia was tested using the hot-plate and tail-flick tests. For the hot-plate test, animals were tested in late pregnancy (Day 17 or Day 18 of pregnancy; mice deliver on Day 19) and in the postpartum period (Days 2 and 8 after delivery) in the following groups: i) no treatment (n = 15); ii) vehicle only (n = 15); iii) SCH 32615 250 mg/kg (n = 20), 150 mg/kg (n = 15), 50 mg/kg (n = 14); iv) naloxone 5 mg/kg (n = 15); v) naloxone 5 mg/kg+SCH 32615 150 mg/kg (n = 10); vi) nonpregnant control given SCH 32615 150 mg/kg (n = 14). All drugs were given subcutaneously. Hot-plate latency (HPL) was significantly higher in pregnant mice (mean hot-plate latency 17.5 s) than postpartum mice (mean hot-plate latency 11 s on Day 2 and 8.5 s on Day 8). SCH 32615 250 mg/kg and 150 mg/kg significantly enhanced this analgesia in pregnant mice (mean percent of maximum possible effect 24.2 and 29.9, respectively) but not SCH 32615 50 mg/kg or the vehicle alone (mean percent of maximum possible effect 12.4 and 0.5, respectively). Naloxone significantly lowered HPL in pregnant mice (19.8 s-16.2 s) and antagonized the effect of SCH 32615.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of SCH 32615, an enkephalinase inhibitor, on D-1 and D-2 dopamine receptor-mediated behaviors
Neuropharmacology 1995 Jun;34(6):677-82.PMID:7566505DOI:10.1016/0028-3908(95)00026-3.
Striatal enkephalin-containing neurons receive dopaminergic inputs from the substantia nigra and project to the external segment of globus pallidus. These neurons express primarily dopamine (DA) D-2 receptors. Accordingly, stimulation of enkephalinergic transmission might be expected to influence mainly D-2 receptor agonist or antagonist effects on motor function. To test this hypothesis, the effects of SCH 32615, an enkephalinase inhibitor, on DA antagonist-induced catalepsy, DA D-1 agonist-induced non-stereotyped grooming, and DA D-2 agonist-induced stereotyped behavior were studied. The administration of SCH 32615 (3 mg/kg) decreased both D-1 and D-2 antagonist-induced catalepsy. In contrast, SCH 32615 (0.3 mg/kg) increased D-1 agonist-induced non-stereotyped grooming and D-2 agonist-induced stereotypies. These results suggest that a DA agonist-like, mostly D-2 activity may be involved in enkephalinergic-mediated functions.
Pharmacology of SCH 34826, an orally active enkephalinase inhibitor analgesic
J Pharmacol Exp Ther 1988 Jun;245(3):829-38.PMID:3164388doi
SCH 34826 [(S)-N-[N-[1-[[(2,2-dimethyl-1,3-dioxolan-4yl) methoxy]carbonyl]-2-phenylethyl]-L-phenylalanine]-beta-alanine] was synthesized as a p.o. active prodrug enkephalinase inhibitor. In vivo, it is de-esterified to SCH 32615 (N-[L-(-1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine), the active constituent. In vitro, the Ki for SCH 32615 to block the degradation of Met5-enkephalin by isolated enkephalinase is 19.5 +/- 0.9 nM. In contrast, SCH 32615 did not inhibit aminopeptidase or diaminopeptidase III degradation of Met5-enkephalin up to 10 microM and did not affect angiotensin converting enzyme up to 10 microM. In vivo, p.o. administered SCH 34826 potentiated the analgesic effects of D-Ala2-Met5-enkephalinamide in mice (ED50 = 5.3 mg/kg p.o.) and rats [minimal effective dose (MED) = 1 mg/kg p.o.]; SCH 32615 had no effect up to 30 mg/kg p.o., but was active parenterally (ED50 in mice = 1.4 ng/kg sc). Direct, naloxone-reversible analgesic effects of SCH 34826 were demonstrated in the mouse low temperature hot-plate test (MED = 30 mg/kg p.o.), the mouse acetic acid-induced writhing test (MED = 30 mg/kg p.o.), the rat stress-induced analgesia test (MED = 10 mg/kg p.o.) and the modified rat yeast-paw test (MED = 100 mg/kg p.o.). Using the rat D-Ala2-Met5-enkephalinamide potentiation test the duration of action of SCH 34826 was at least 4 hs. No respiratory or gastrointestinal side effects of any consequence were noted at doses up to 100 times those active in the D-Ala2-Met-5-enkephalinamide potentiation test.
Analgesic and acute central nervous system side effects of the intravenously administered enkephalinase inhibitor SCH 32615
Pharmacol Biochem Behav 1991 Jan;38(1):21-7.PMID:2017447DOI:10.1016/0091-3057(91)90584-o.
The analgesic and acute central nervous system (CNS) side effect potential of the enkephalinase inhibitor SCH 32615 (N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenyl-alanine-beta-alanine) were evaluated after IV administration to mice, rats and squirrel monkeys. In mice, SCH 32615 caused dose-related suppression of acetic acid-induced writhing (minimal effective dose, MED = 3 mg/kg IV). In rats, SCH 32615 produced dose-related increases in the response latencies in the yeast inflamed-paw test (MED = 10 mg/kg IV). In squirrel monkeys, using a new hot-water bath tail-flick test, SCH 32615 significantly prolonged the escape latencies (MED = 100 mg/kg IV). These results in primates are the first data showing an analgesic action of an enkephalinase inhibitor in a reflex model of pain. When measured for its CNS side effect potential, SCH 32615 had no significant effects in rats (up to 100 times its analgesically active doses) or in monkeys (up to three times). In the mouse, at doses 100 times its minimal effective dose, SCH 32615 produced brief convulsions; these lasted only a minute, resolved quickly, and did not cause lethality. In contrast, in rats and squirrel monkeys, the standard opioid analgesic morphine produced profound CNS side effects; this was particularly notable in monkeys, in which morphine's maximal analgesic effects were associated with near lethal respiratory depression. These data demonstrate that SCH 32615 produces selective analgesic actions and that its acute side effect liability is less than that seen with a clinically used standard.
Acute toxicology of an enkephalinase inhibitor (SCH 32615) given intrathecally in the ewe
Anesth Analg 1993 Jan;76(1):123-30.PMID:8418713DOI:10.1213/00000539-199301000-00022.
Intrathecal application of the enkephalinase inhibitor, SCH 32615, yields antinociception in animal paradigms. Our purpose was to identify possible acute behavioral effects, neurotoxicity, or systemic toxicity of intrathecal SCH 32615 administration during 9 days in the ewe. Seventeen ewes were implanted with lumbar silicone intrathecal catheters and subcutaneous access ports for repeated injection. Baseline and serial daily behavioral assessments were made during 9 days of 2-mL intrathecal injection twice daily of either normal saline (SAL group) or a 20 mg/mL isotonic sterile solution of SCH 32615 (SCH group). Data were analyzed by treatment group (SCH versus SAL) by taking the group means of individual ewe cumulative scores during 9 days. At 15-18 h after the last injection, the ewes were euthanized and the spinal cords and leptomeninges were grossly examined and prepared for histological assessment. Histological evaluation of the lumbar (at catheter entrance site and catheter tip), thoracic, and cervical sections of all animals was performed by two neuropathologists. Several mild, reversible, and apparently nonprogressive behaviors (Stepping/Placing and Hindlimb Stretching/Splaying) were observed almost exclusively in SCH-treated ewes. These behaviors were interpreted as mild temporary irritative effects, without significant neuropathological sequelae. Pathological findings primarily consisted of mild, focal dural thickening and white matter compression. These changes were distributed equally between drug-treated and control groups and were attributable to catheter implantation and local compressive effects. There were no pathological bases identified in this study to preclude the clinical study of SCH 32615 within the dose range studied.