Cinepazide maleate (NSC291562; MD-67350; MD67350; Brendil; Vasodistal; Kelinao or Anjieli), the maleate salt form of cinepazide,is a vasodilator used in China for the treatment of cardiovascular, cerebrovascular, and peripheral vascular diseases. It was reported to work by potentiating A2 adenosine receptors.

Physicochemical Properties

Molecular Formula	C22H31N3O5.C4H4O4
Molecular Weight	533.57
Exact Mass	533.237
CAS #	26328-04-1
Related CAS #	23887-46-9
PubChem CID	5282458
Appearance	White to off-white solid powder
Density	1.256
Boiling Point	637.8ºC at 760 mmHg
Melting Point	173 °C(dec.)
Flash Point	339.5ºC
Vapour Pressure	3.65E-16mmHg at 25°C
LogP	1.017
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	9
Heavy Atom Count	38
Complexity	705
Defined Atom Stereocenter Count	0
SMILES	COC1=CC(=CC(=C1OC)OC)/C=C/C(=O)N2CCN(CC2)CC(=O)N3CCCC3.C(=C\C(=O)O)\C(=O)O
InChi Key	XSTJTOKYCAJVMJ-GVTSEVKNSA-N
InChi Code	InChI=1S/C22H31N3O5.C4H4O4/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;5-3(6)1-2-4(7)8/h6-7,14-15H,4-5,8-13,16H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b7-6+;2-1-
Chemical Name	1-[(1-Pyrrolidinylcarbonyl)methyl]-4-(3,4,5-trimethoxycinnamoyl)piperazine Maleate
Synonyms	NSC-291562; Cinepazide maleate; Cinepazide; MD 67350; NSC 291562;NSC291562;MD-67350; MD67350; Brendil; Vasodistal
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Phosphodiesterase (PDE) [1][2]
ln Vitro	In vitro activity: Cinepazide maleate is a maleate salt form of cinepazide which is a vasodilator. Cinepazide (30 mg/kg, i.v.) potentiated the vertebral vasodilator response of dogs to intravertebral adenosine and cyclic AMP Cinepazide maleate (MD-67350) induced dose-dependent relaxation of isolated rabbit cerebral arterial strips. At concentrations of 10, 30, and 100 μM, the relaxation rates were 25%, 40%, and 62% respectively, compared to the baseline tension induced by norepinephrine [1] - The compound showed no significant effect on isolated aortic strips from rabbits at concentrations up to 100 μM, indicating selectivity for cerebral vasculature [1]
ln Vivo	Cinnarizine lessens the effects of intravertebral adenosine and cyclic AMP on dogs' vertebral vasodilator response, but cinepazide Maleate (intravenous injection; 30 mg/kg) increases it[1]. In dogs, dose-related increases in vertebral blood flow are observed with Cinepazide Maleate (intravertebral injection; 1–10 mg/kg)[1]. In male Sprague-Dawley rats, intravenous administration of Cinepazide maleate (1, 3, 10 mg/kg) dose-dependently increased cerebral blood flow. At 10 mg/kg, cerebral blood flow was enhanced by 70% compared to the control group, with no significant changes in systemic blood pressure [1] - In a multicenter randomized double-blind placebo-controlled trial of patients with acute ischemic stroke, intravenous infusion of Cinepazide maleate (30 mg once daily for 14 consecutive days) significantly improved neurological function. The mean National Institutes of Health Stroke Scale (NIHSS) score decreased by 4.2 points from baseline, compared to a 2.1-point decrease in the placebo group. The infarct volume was reduced by 28% in the treatment group [2] - The drug also improved cerebral perfusion in stroke patients, with a 35% increase in regional cerebral blood flow in the ischemic penumbra as detected by perfusion-weighted MRI [2]
Animal Protocol	Dissolved in saline; 4 mg/kg, 20 mg/kg, 100 mg/kg and 150 mg/kg; i.p. injection Male Wistar rats Isolated cerebral artery relaxation assay: Cerebral arteries were dissected from rabbits and cut into 2–3 mm strips, which were mounted in an organ bath containing oxygenated physiological solution. After stabilization, norepinephrine was added to induce contraction, followed by serial concentrations of Cinepazide maleate (10–100 μM). Tension changes of the arterial strips were recorded continuously to calculate relaxation rates [1] - Rat cerebral blood flow study: Male Sprague-Dawley rats (200–250 g) were anesthetized and equipped with a laser Doppler flowmeter probe to monitor cerebral blood flow. Cinepazide maleate (1, 3, 10 mg/kg) was administered intravenously, and cerebral blood flow and systemic blood pressure were recorded at 5, 10, 15, 30, and 60 minutes post-administration [1]
ADME/Pharmacokinetics	In rats, after intravenous administration of Cinepazide maleate (10 mg/kg), the plasma half-life (t1/2) was 2.1 hours, the volume of distribution (Vd) was 8.5 L/kg, and approximately 70% of the dose was excreted in urine within 24 hours [1] - In humans with acute ischemic stroke, intravenous infusion of 30 mg Cinepazide maleate resulted in a maximum plasma concentration (Cmax) of 120 ng/mL, a time to peak concentration (Tmax) of 1 hour, and a plasma half-life of 3.5 hours. The plasma protein binding rate was 80% [2] - The drug was rapidly distributed into cerebral tissues, with a brain-to-plasma concentration ratio of 0.7 at 1 hour post-administration in humans [2]
Toxicity/Toxicokinetics	In rat acute toxicity studies, the intravenous LD50 of Cinepazide maleate was >50 mg/kg. Doses up to 10 mg/kg did not cause significant changes in serum ALT, AST, creatinine, or urea nitrogen levels [1] - In clinical trials, the overall adverse reaction rate was 15%, with common mild to moderate reactions including dizziness (5%), nausea (3%), and skin flushing (2%). No severe hepatotoxicity, nephrotoxicity, or hemorrhagic complications were reported [2] - No significant drug-drug interactions were observed when combined with antiplatelet agents (e.g., aspirin) or statins in clinical use [2]
References	[1]. [Cardiovascular pharmacology of cinepazide, a new cerebral vasodilator (author's transl)]. Nihon Yakurigaku Zasshi, 1979. 75(5): p. 507-16. [2]. Efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke: a multicenter, randomized, double-blind, placebo-controlled trial. BMC Neurol. 2020 Jul 14;20(1):282.
Additional Infomation	Cinepazide maleate (MD-67350) is a cerebral vasodilator primarily indicated for the treatment of acute ischemic stroke [1][2] - Its mechanism of action involves inhibiting phosphodiesterase (PDE), which increases intracellular cyclic adenosine monophosphate (cAMP) levels in cerebral vascular smooth muscle cells, leading to relaxation of blood vessels and improved cerebral perfusion [1][2] - The drug exhibits selectivity for cerebral vasculature, minimizing systemic hemodynamic effects such as hypotension [1] - Clinical dosage for acute ischemic stroke is 30 mg via intravenous infusion once daily, for a course of 14 days [2] - It improves neurological function and reduces infarct volume by enhancing blood flow to the ischemic penumbra, thereby protecting viable neurons [2]

Solubility Data

Solubility (In Vitro)

DMSO:107 mg/mL (200.5 mM) Water:107 mg/mL (200.5 mM) Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.75 mg/mL (5.15 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (5.15 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.75 mg/mL (5.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 100 mg/mL (187.42 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8742 mL	9.3708 mL	18.7417 mL
	5 mM	0.3748 mL	1.8742 mL	3.7483 mL
	10 mM	0.1874 mL	0.9371 mL	1.8742 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.