Cinepazide

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Cinepazide
Cinepazide.svg
Clinical data
ATC code
Identifiers
  • (2E)-1-{4-[2-Oxo-2-(1-pyrrolidinyl)ethyl]-1-piperazinyl}-3-(3,4,5-trimethoxyphenyl)-2-propen-1-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.041.739 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H31N3O5
Molar mass 417.49864 g·mol−1
3D model (JSmol)
  • O=C(N1CCCC1)CN3CCN(C(=O)\C=C\c2cc(OC)c(OC)c(OC)c2)CC3
  • InChI=1S/C22H31N3O5/c1-28-18-14-17(15-19(29-2)22(18)30-3)6-7-20(26)25-12-10-23(11-13-25)16-21(27)24-8-4-5-9-24/h6-7,14-15H,4-5,8-13,16H2,1-3H3/b7-6+ X mark.svgN
  • Key:RCUDFXMNPQNBDU-VOTSOKGWSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Cinepazide or cinepazide maleate [1] (Kelinao or Anjieli in China [2] [3] ) is a vasodilator used in China for the treatment of cardiovascular and cerebrovascular diseases, and peripheral vascular diseases. [4] It appears to work by potentiating A2 adenosine receptors. [5]

History

Cinepazide was discovered by scientists at Laboratoires Delalande (now part of Sanofi) in 1969 in an effort to explore useful substituted cinnamoyl-piperazine compounds. [6] [7] The drug, in the form of a pill taken orally, was launched by Delalande in 1976 under the tradename Vasodistal, for treatment of heart failure, balance disorders, cerebrovascular disease, and vascular complications of diabetes. [6] [8] In 1988 the drug was withdrawn from the market in Spain due to risk of agranulocytosis; other countries where the drug was available added warnings to the label. [9] [10] It was withdrawn from the market in France in 1992. [11] The drug had also been marketed in Japan by Daiichi Pharmeceutical Company under the brand name "Brindel" [2] for dementia, but was withdrawn in 1999, following a review by the Japanese regulatory authorities of dementia drugs after a drug, calcium hopantenate, that had been considered the standard of care and against which cinepazide and other dementia drugs had been compared, had failed to demonstrate efficacy in a re-evaluation. [12]

In 2002 Sihuan Pharmaceutical brought an injectable form of the drug to market in China; [13] Sihuan had acquired the drug from a military hospital in China that had developed the formulation. [14] In 2010 it was the highest selling drug in China, with about 1 billion RMB in sales in the 3rd quarter, outselling Plavix in China. [13] [3] This made Sihuan Pharm the largest company in China in the cardio-cerebral vascular drug market in 2010. [3] In 2014 it was the tenth highest-selling drug in China. [14]

Related Research Articles

Vascular dementia (VaD) is dementia caused by problems in the blood supply to the brain, resulting from a cerebrovascular disease. Restricted blood supply (ischemia) leads to cell and tissue death in the affected region, known as an infarct. The three types of vascular dementia are subcortical vascular dementia, multi-infarct dementia, and stroke related dementia. Subcortical vascular dementia is brought about by damage to the small blood vessels in the brain. Multi-infarct dementia is brought about by a series of mini-strokes where many regions have been affected. The third type is stroke related where more serious damage may result. Such damage leads to varying levels of cognitive decline. When caused by mini-strokes, the decline in cognition is gradual. When due to a stroke, the cognitive decline can be traced back to the event.

<span class="mw-page-title-main">Cerebrovascular disease</span> Condition that affects the arteries that supply the brain

Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. The most common presentation of cerebrovascular disease is an ischemic stroke or mini-stroke and sometimes a hemorrhagic stroke. Hypertension is the most important contributing risk factor for stroke and cerebrovascular diseases as it can change the structure of blood vessels and result in atherosclerosis. Atherosclerosis narrows blood vessels in the brain, resulting in decreased cerebral perfusion. Other risk factors that contribute to stroke include smoking and diabetes. Narrowed cerebral arteries can lead to ischemic stroke, but continually elevated blood pressure can also cause tearing of vessels, leading to a hemorrhagic stroke.

<span class="mw-page-title-main">Piracetam</span> Chemical compound

Piracetam is a drug marketed as a treatment for myoclonus. It is also used as a cognitive enhancer to improve memory, attention, and learning. Evidence to support its use is unclear, with some studies showing modest benefits in specific populations and others showing minimal or no benefit. Piracetam is sold as a medication in many European countries. Sale of piracetam is not illegal in the United States, although it is not regulated nor approved by the FDA so it is legally sold for research use only.

<span class="mw-page-title-main">Ramipril</span> ACE inhibitor

Ramipril, sold under the brand name Altace among others, is an ACE inhibitor type medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It can also be used as a preventative medication in patients over 55 years old to reduce the risk of having a heart attack, stroke or cardiovascular death in patients shown to be at high risk, such as some diabetics and patients with vascular disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth.

<span class="mw-page-title-main">Valsartan</span> Angiotensin II receptor antagonist

Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination valsartan/hydrochlorothiazide, valsartan/amlodipine, valsartan/amlodipine/hydrochlorothiazide, or valsartan/sacubitril.

<span class="mw-page-title-main">Nicergoline</span> Chemical compound

Nicergoline, sold under the brand name Sermion among others, is an ergot derivative used to treat senile dementia and other disorders with vascular origins. Internationally it has been used for frontotemporal dementia as well as early onset in Lewy body dementia and Parkinson's dementia. It decreases vascular resistance and increases arterial blood flow in the brain, improving the utilization of oxygen and glucose by brain cells. It has similar vasoactive properties in other areas of the body, particularly the lungs. Unlike many other ergolines, such as ergotamine, nicergoline is not associated with cardiac fibrosis.

<span class="mw-page-title-main">Isoxsuprine</span> Group of stereoisomers

Isoxsuprine is a drug used as a vasodilator in humans and equines. Isoxsuprine is a β2 adrenoreceptor agonist that causes direct relaxation of uterine and vascular smooth muscle via β2 receptors.

<span class="mw-page-title-main">Tandospirone</span> Anxiolytic and antidepressant medication

Tandospirone, sold under the brand name Sediel, is an anxiolytic and antidepressant medication used in Japan and China, where it is marketed by Dainippon Sumitomo Pharma. It is a member of the azapirone class of drugs and is closely related to other azapirones like buspirone and gepirone.

Benfluorex, sold under the brand name Mediator, is an anorectic and hypolipidemic agent that is structurally related to fenfluramine. It may improve glycemic control and decrease insulin resistance in people with poorly controlled type-2 diabetes.

<span class="mw-page-title-main">Prenylamine</span> Chemical compound

Prenylamine (Segontin) is a calcium channel blocker of the amphetamine chemical class that was used as a vasodilator in the treatment of angina pectoris.

<span class="mw-page-title-main">Flupirtine</span> Non-opioid analgesic

Flupirtine is an aminopyridine that functions as a centrally acting non-opioid analgesic that was originally used as an analgesic for acute and chronic pain but in 2013 due to issues with liver toxicity, the European Medicines Agency restricted its use to acute pain, for no more than two weeks, and only for people who cannot use other painkillers. In March 2018, marketing authorisations for flupirtine were withdrawn following a European Medicines Agency recommendation based on the finding that the restrictions introduced in 2013 had not been sufficiently followed in clinical practice, and cases of serious liver injury still occurred including liver failure.

<span class="mw-page-title-main">Dotarizine</span> Calcium channel blocker used in the treatment of migraine

Dotarizine is a drug used in the treatment of migraine, which acts as a calcium channel blocker, and also as an antagonist at the 5HT2A receptor, and to a lesser extent at the 5HT1A and 5HT2C receptors. The anti-migraine action is thought to be due to its action as a vasodilator, but it also has some anxiolytic effects and blocks amnesia produced by electroconvulsive shock in animals.

<span class="mw-page-title-main">Caroverine</span> Chemical compound

Caroverine is a muscle-relaxing drug used in Austria and Switzerland to relieve spasms in smooth muscles, and the use in those countries was extended to aid with cerebrovascular diseases there, and eventually to treat tinnitus. It is also used to treat tinnitus in India.

<span class="mw-page-title-main">Pimavanserin</span> Atypical antipsychotic medication

Pimavanserin, sold under the brand name Nuplazid, is an atypical antipsychotic which is approved for the treatment of Parkinson's disease psychosis and is also being studied for the treatment of Alzheimer's disease psychosis, schizophrenia, agitation, and major depressive disorder. Unlike other antipsychotics, pimavanserin is not a dopamine receptor antagonist.

<span class="mw-page-title-main">Complications of hypertension</span>

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<span class="mw-page-title-main">Fabomotizole</span> Chemical compound

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<span class="mw-page-title-main">Indacaterol/glycopyrronium bromide</span> Combination drug

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<span class="mw-page-title-main">Hypertension and the brain</span>

Hypertension is a condition characterized by an elevated blood pressure in which the long term consequences include cardiovascular disease, kidney disease, adrenal gland tumors, vision impairment, memory loss, metabolic syndrome, stroke and dementia. It affects nearly 1 in 2 Americans and remains as a contributing cause of death in the United States. There are many genetic and environmental factors involved with the development of hypertension including genetics, diet, and stress.

References

  1. "Anjieli, Kelinao, cinepazide maleate - Product Profile - BioCentury". www.biocentury.com. Retrieved 2015-08-04.
  2. 1 2 Drugs.com Drugs.com International listings for cinepazide Page accessed Aug 3, 2015
  3. 1 2 3 20 Oct 2010 Sihuan Pharm – China's leading player in cardio-cerebral vascular drug – IPO Report Archived 2015-09-23 at the Wayback Machine
  4. Sihuan Pharmaceutical Kelinao/Anjieli official site Page accessed Aug 3, 2015
  5. Ruffolo RR, Hieble JP, Brooks DP, Feuerstein GZ, Nichols AJ (1991). "Drug receptors and control of the cardiovascular system: recent advances" . Progress in Drug Research. Fortschritte der Arzneimittelforschung. Progrès des Recherches Pharmaceutiques. 36: 117–360. doi:10.1007/978-3-0348-7136-5_4. ISBN   978-3-0348-7138-9. PMID   1876708.
  6. 1 2 Johnson Sun for Guotai Junan International. Sept 28, 2011. Company Report: Sihuan Pharmaceuticals
  7. Cameron BD, Chasseaud LF, Hawkins DR, Taylor T (July 1976). "The metabolic fate of the coronary vasodilator 4-(3,4,5-Trimethoxycinnamoyl)-1-(N-pyrrolidinocarbonylmethyl)piperazine (cinepazide) in the rat, dog and man". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 6 (7): 441–55. doi:10.3109/00498257609151657. PMID   997590.
  8. Reactions Weekly 305(1):1. June 1990 Cinepazide-related agranulocytosis
  9. Laporte JR, Capellà D, Juan J (1990). "Agranulocytosis induced by cinepazide". European Journal of Clinical Pharmacology. 38 (4): 387–8. doi:10.1007/bf00315580. PMID   2344862. S2CID   19427552.
  10. Department of Economic and Social Affairs of the United Nations Secretariat Consolidated List of Products Whose Consumption and/or Sale Have Been Banned, Withdrawn, Severely Restricted or not Approved by Governments Twelfth Issue: Pharmaceuticals United Nations – New York, 2005
  11. Sidney M. Wolfe, M.D. for the Public Citizen's Health Research Group. February 2, 1995. Differences in the Number of Drug Safety Withdrawals: United States, United Kingdom, Germany and France 1970-1992
  12. Takeda M, Tanaka T, Okochi M (August 2011). "New drugs for Alzheimer's disease in Japan". Psychiatry and Clinical Neurosciences. 65 (5): 399–404. doi:10.1111/j.1440-1819.2011.02253.x. PMID   21851448. S2CID   21519637.
  13. 1 2 Lefei Sun, Jinsong Du, and Iris Wang for Credit Suisse. October 6, 2011 China Pharma Sector
  14. 1 2 Su Zhang for Standard Chartered Bank (HK) Limited. June 27, 2014 China health care: Pharma sector comes of age