Terlipressin acetate is a white or almost white powder or crystalline solid, odorless. Molecular formula C52H74N16O15S2, CAS 14636-12-5, molecular weight 1287.43, belongs to macromolecular compounds. Soluble in water, almost insoluble in organic solvents such as chloroform, ether, and ethyl acetate. The dissolution process in water is an endothermic process that requires the absorption of a large amount of heat. Therefore, warm water or heating can be used to improve the dissolution rate and solubility during dissolution. It has hygroscopicity and is prone to moisture absorption in the air, leading to drug clumping, deliquescence, etc. Therefore, during storage and transportation, it is necessary to maintain a dry environment and avoid contact with environments with high humidity. It is an artificially synthesized peptide drug with multiple important physiological and pharmacological effects.
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Customized Bottle Caps And Corks:
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Chemical Formula |
C52H74N16O15S2 |
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Exact Mass |
1226 |
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Molecular Weight |
1227 |
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m/z |
1226 (100.0%), 1227 (56.2%), 1229 (15.5%), 1228 (9.0%), 1227 (5.9%), 1229 (5.1%), 1228 (3.3%), 1229 (3.1%), 1230 (2.8%), 1230 (1.7%), 1227 (1.6%), 1230 (1.4%) |
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Elemental Analysis |
C, 50.89; H, 6.08; N, 18.26; O, 19.55; S, 5.22 |
Terlipressin Acetate is a synthetic vasoconstrictor commonly used in the treatment of liver cirrhosis, portal hypertension, and related complications.
1. Non selective V1 receptor agonists:
It is considered a non selective V1 receptor agonist. V1 receptor is a receptor that exists on vascular smooth muscle cells, and its activation can lead to vascular smooth muscle contraction. When Terlipressin binds to the V1 receptor, it mimics the natural antidiuretic hormone arginine vasopressin (AVP), causing vasoconstriction effects. This contraction mainly occurs in the surrounding blood vessels and visceral blood vessels, especially in the portal vein system.
2. Vasoconstrictive effect:
The vasoconstriction effect is achieved by stimulating the V1 receptor on vascular smooth muscle cells. When this substance binds to the V1 receptor, it promotes the contraction of vascular smooth muscle cells, leading to vasoconstriction. This contraction effect can affect blood vessels throughout the body, especially visceral blood vessels. By increasing total peripheral resistance, visceral congestion and edema caused by portal hypertension can be effectively alleviated.
3. Diversion effect:
In addition to direct vasoconstriction, it also has a shunt effect. Patients with portal hypertension often experience abnormal increases in portal venous system blood flow, which may lead to blood accumulation in the liver and liver dysfunction. Using can reduce the blood flow in the portal vein system, thereby guiding blood through other diversion pathways, such as collateral circulation. In this way, it can alleviate the adverse effects of portal hypertension on the liver.
4. Inhibition of endotoxin absorption:
Patients with portal hypertension often experience an increase in intestinal mucosal permeability, leading to the entry of endotoxins (toxic substances produced by bacteria) into the systemic circulation. The presence of these endotoxins may lead to serious complications, such as bacterial infections, imbalance of gut microbiota, etc. The use of this substance is believed to reduce the increase in intestinal mucosal permeability, thereby reducing the absorption of endotoxins. This may help prevent and alleviate complications associated with portal hypertension.
Specific steps:
Terlipressin acetate is an artificially synthesized peptide drug that can be prepared through laboratory synthesis methods.
Selecting starting materials:
Amino resin is usually chosen as the starting material, and amino acid residues are connected to the resin through solid-phase peptide synthesis technology.
Protecting the synthesis of amino acids:
Select the required amino acids and protect them to prevent side reactions during the synthesis process. Common protective groups include Boc (tert butoxycarbonyl), Alloc (allyl oxycarbonyl), etc.
Growth of peptide chain:
Connect amino acid residues to the solid-phase carrier in the desired sequence, forming a linear peptide chain. Each step of the reaction needs to ensure that highly active amino groups are protected to avoid unnecessary side reactions.
Protection of side chain allyl groups:
In some cases, to prevent side chain allyl groups from experiencing side reactions during the synthesis process, allyl protection is necessary. Common protective groups include trifluoroacetyl and chloroacetyl groups.
Deprotection reaction:
After completing the cyclization reaction on the desired amino acid residue, a deprotection reaction is carried out to remove the protective groups on the protected amino acid residue. Common deprotection reagents include TFA (trifluoroacetic acid) or HCl.
Cyclization reaction:
Transforming linear peptide chains into cyclic structures is one of the key steps in the synthesis of product. Cyclization can be achieved through different methods, such as forming ester bonds, amide bonds, etc. The commonly used cyclization method is to connect one end of the peptide chain to the other end, forming a circular structure.
Cutting and purification:
Cut peptide chains from solid-phase carriers and purify them to remove unreacted raw materials and by-products. Common cutting reagents include TFA (trifluoroacetic acid) or HCl, etc. Purification is usually achieved through column chromatography or crystallization.
Quality testing and control:
The synthesized Terlipresin Acetate is subjected to quality testing and control through analytical methods such as mass spectrometry and high-performance liquid chromatography to ensure that its purity and quality meet the requirements.
Terlipressin, an innovative artificially synthesized long-acting vasopressin preparation, represents a major advancement in modern pharmaceutical technology in the field of vasoactive drugs. As a prodrug, terlipressin does not have direct biological activity before it is activated. Instead, it needs to undergo a specific enzymatic hydrolysis process in the body - the action of aminopeptidase - to gradually remove the three glycyl residues at its N-terminus, in order to slowly "unlock" and release the biologically active lysine vasopressin. This unique "slow release" mechanism endows terlipressin with significant pharmacokinetic advantages, allowing it to maintain sustained smooth muscle contraction for up to 10 hours after a single administration. In contrast, the activity maintenance time of traditional vasopressin at the same dose is only 20 to 40 minutes, much shorter than terlipressin.
The pharmacological effects of terlipressin are extensive and profound. It mainly contracts the smooth muscle of visceral blood vessels, effectively reducing blood flow to visceral organs such as the mesentery, spleen, uterus, etc. This mechanism of action is of great significance for reducing portal vein blood flow and relieving portal hypertension. In patients with chronic liver diseases such as cirrhosis, portal hypertension is one of the main causes of esophageal variceal bleeding, and terlipressin is currently the only drug that can significantly improve the survival rate of such patients. By reducing portal vein blood flow, terlipressin can significantly reduce the risk of esophageal variceal bleeding, providing strong protection for the life and health of patients.
In addition, terlipressin Acetate also has a unique effect of reducing plasma renin concentration, which has a significant effect on improving renal function in patients with hepatorenal syndrome. Hepatorenal syndrome is one of the common complications in patients with severe liver diseases such as cirrhosis, characterized by symptoms such as decreased kidney function and decreased urine output. Terlipressin can increase renal blood flow in patients with hepatorenal syndrome by reducing plasma renin concentration, thereby improving renal function, increasing urine output, and helping to improve patient prognosis.
In addition to the main application areas mentioned above, terlipressin has also shown potential therapeutic value in refractory shock and cardiopulmonary resuscitation. In patients with refractory shock, terlipressin can provide important assistance for their life support by constricting blood vessels and increasing blood pressure. During the process of cardiopulmonary resuscitation, terlipressin may also improve cardiac perfusion, increase myocardial contractility, and other mechanisms to gain valuable rescue time for patients.
Compared with traditional vasopressin, terlipressin not only has a long-lasting effect, but also has higher safety. Due to its slow enzymatic hydrolysis rate, the concentration of lysine vasopressin in the circulation remains within a safe range, avoiding the risk of poisoning. Meanwhile, the use of terlipressin is simple and convenient, and can be administered intravenously, making it more suitable for rapid rescue and treatment of critically ill patients.
faq
What is terlipressin acetate used for?
Description. Terlipressin injection is used to improve kidney function in patients with hepatorenal syndrome (kidney problem that occurs in patients with severe liver disease) with rapid change in kidney function. This medicine is to be given only by or under the immediate supervision of your doctor.
What is the mechanism of action of terlipressin?
Vasoconstriction of splanchnic circulation is the presumed mechanism of action of terlipressin. A delay of several days occurs between the improvement in circulatory function and the increase in GFR. Concurrent systemic vasoconstriction may potentially cause ischemic side effects.
Is terlipressin a V1 agonist?
As a V1 agonist, terlipressin increases systemic vascular resistance, particularly in the splanchnic area, resulting in a decrease of portal pressure. V1 binding also promotes platelet aggregation and glycogenolysis, while V3 binding induces adrenocorticotropic hormone (ACTH) secretion.
How does terlipressin stop bleeding?
It mainly acts on the V1 receptors which are predominantly located in the arterial smooth muscle within the splanchnic circulation, thereby reducing the splanchnic blood flow and portal pressure and controlling AVB. Several meta-analyses about terlipressin for AVB have been published (Supplementary Table 1).
What are the side effects of terlipressin?
Cardiac disorders: Tachycardia, bradycardia, pulmonary oedema, dyspnoea. Gastrointestinal disorders: Intestinal ischaemia, abdominal cramps, diarrhea, nausea, vomiting. Metabolism and nutrition disorders: Rarely, hyponatraemia, hyperglycaemia. Nervous system disorders: Convulsion, headache.
What is the best treatment for liver cirrhosis?
This usually involves treating the cause, for example, antiviral medicines if it's caused by hepatitis B or C. You usually also have treatment to help prevent and treat complications of cirrhosis. This may include: laxative medicine to help remove toxins from your body.
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