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药品详细

Nimodipine(尼莫地平)

化学结构式图
中文名
尼莫地平
英文名
Nimodipine
分子式
C21H26N2O7
化学名
3-(2-methoxyethyl) 5-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
分子量
Average: 418.4403
Monoisotopic: 418.174001196
CAS号
66085-59-4
ATC分类
C08C 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Nimodipine is a 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, nimodipine prevents calcium-dependent smooth muscle contraction and subsequent vasoconstriction. Compared to other calcium channel blocking agents, nimodipine exhibits greater effects on cerebral circulation than on peripheral circulation. Nimodipine is used to as an adjunct to improve the neurologic outcome following subarachnoid hemorrhage from ruptured intracranial aneurysm.

生产厂家
  • Banner pharmacaps inc
  • Barr laboratories inc
  • Bayer pharmaceuticals corp
  • Sun pharmaceutical industries inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Janjua N, Mayer SA: Cerebral vasospasm after subarachnoid hemorrhage. Curr Opin Crit Care. 2003 Apr;9(2):113-9. Pubmed
  2. Allen GS, Ahn HS, Preziosi TJ, Battye R, Boone SC, Boone SC, Chou SN, Kelly DL, Weir BK, Crabbe RA, Lavik PJ, Rosenbloom SB, Dorsey FC, Ingram CR, Mellits DE, Bertsch LA, Boisvert DP, Hundley MB, Johnson RK, Strom JA, Transou CR: Cerebral arterial spasm—a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med. 1983 Mar 17;308(11):619-24. Pubmed
  3. Belfort MA, Anthony J, Saade GR, Allen JC Jr: A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia. N Engl J Med. 2003 Jan 23;348(4):304-11. Pubmed#
    Kim JH, Park IS, Park KB, Kang DH, Hwang SH: Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2009 Sep;46(3):239-44. Epub 2009 Sep 30. Pubmed
  4. Tomassoni D, Lanari A, Silvestrelli G, Traini E, Amenta F: Nimodipine and its use in cerebrovascular disease: evidence from recent preclinical and controlled clinical studies. Clin Exp Hypertens. 2008 Nov;30(8):744-66. Pubmed
  5. Vergouwen MD, Vermeulen M, Roos YB: Effect of nimodipine on outcome in patients with traumatic subarachnoid haemorrhage: a systematic review. Lancet Neurol. 2006 Dec;5(12):1029-32. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Nitrobenzenes
Substructures
  • Dihydropyridines
  • Carboxylic Acids and Derivatives
  • Nitrobenzenes
  • Acetates
  • Oxoazaniums
  • Ethers
  • Benzene and Derivatives
  • Nitro compounds
  • Enamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anilines
适应症
药理
Indication For use as an adjunct to improve neurologic outcome following subarachnoid hemorrhage (SAH) from ruptured intracranial berry aneurysms by reducing the incidence and severity of ischemic deficits.
Pharmacodynamics Nimodipine belongs to the class of pharmacological agents known as calcium channel blockers. Nimodipine is indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured congenital aneurysms who are in good neurological condition post-ictus (e.g., Hunt and Hess Grades I-III). The contractile processes of smooth muscle cells are dependent upon calcium ions, which enter these cells during depolarization as slow ionic transmembrane currents. Nimodipine inhibits calcium ion transfer into these cells and thus inhibits contractions of vascular smooth muscle. In animal experiments, nimodipine had a greater effect on cerebral arteries than on arteries elsewhere in the body perhaps because it is highly lipophilic, allowing it to cross the blood brain barrier.
Mechanism of action Although the precise mechanism of action is not known, nimodipine blocks intracellular influx of calcium through voltage-dependent and receptor-operated slow calcium channels across the membranes of myocardial, vascular smooth muscle, and neuronal cells. Nimodipine binds specifically to L-type voltage-gated calcium channels. The inhibition of calcium ion transfer results in the inhibition of vascular smooth muscle contraction. Evidence suggests that the dilation of small cerebral resistance vessels, with a resultant increase in collateral circulation, and/or a direct effect involving the prevention of calcium overload in neurons may be responsible for nimodipine's clinical effect in patients with subarachnoid hemorrhage.
Absorption In humans, nimodipine is rapidly absorbed after oral administration, and peak concentrations are generally attained within one hour. Bioavailability is 100% following intravenous administration and 3-30% following oral administration due to extensive first-pass metabolism.
Volume of distribution Not Available
Protein binding 95% bound to plasma protein
Metabolism
Hepatic metabolism via CYP 3A4.
Route of elimination Nimodipine is eliminated almost exclusively in the form of metabolites and less than 1% is recovered in the urine as unchanged drug. Numerous metabolites, all of which are either inactive or considerably less active than the parent compound, have been identified.
Half life 1.7-9 hours
Clearance Not Available
Toxicity Symptoms of overdosage would be expected to be related to cardiovascular effects such as excessive peripheral vasodilation with marked systemic hypotension.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00380 Nimodipine Pathway SMP00380
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 125 °C Not Available
logP 3.05 MASUMOTO,K ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 1.20e-02 g/l ALOGPS
logP 3.41 ALOGPS
logP 2.54 ChemAxon
logS -4.5 ALOGPS
pKa (strongest basic) 5.41 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 119.68 ChemAxon
rotatable bond count 10 ChemAxon
refractivity 112.38 ChemAxon
polarizability 43.17 ChemAxon
药物相互作用
Drug Interaction
Cimetidine Cimetidine increases the effect of the calcium channel blocker, nimodipine.
Quinupristin This combination presents an increased risk of toxicity
Telithromycin Telithromycin may reduce clearance of Nimodipine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Nimodipine if Telithromycin is initiated, discontinued or dose changed.
Thiopental The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Nimodipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Nimodipine if Thiopental is initiated, discontinued or dose changed.
Tipranavir Tipranavir may decrease the metabolism and clearance of the calcium channel blocker, Nimodipine. Monitor for changes in Nimodipine therapeutic and adverse effects if Tipranavir is initiated, discontinued or dose changed.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Valproic Acid Valproic acid increases the effect of nimodipine
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of nimodipine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nimodipine if voriconazole is initiated, discontinued or dose changed.
食物相互作用
  • Grapefruit down regulates post-translational expression of CYP3A4, the major metabolizing enzyme of nimodipine. Grapefruit, in all forms (e.g. whole fruit, juice and rind), can significantly increase serum levels of nimodipine and may cause toxicity. Avoid grapefruit products while on this medication.
  • Take at the same time each day, with or without food, but always in the same manner.

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