Ropivacaine hydrochloride, cas 132112-35-7, molecular formula C17H26N2O.ClH.H2O. The compound is a chiral molecule, it can be optically active, and the ratio of the two chiral isomers is about 1:1. White crystal or crystalline powder, its crystal morphology can be observed through a microscope. It may sometimes have yellow or brown spots as the compound oxidizes in the air. The solubility in water is 27.5mg/mL at 20°C, and the solubility is better when the pH is 4.5-5.5. In addition, it also has good solubility in ethanol and methanol. A cationic compound that exists as a salt in water. This is due to the attraction between a positively charged amine group and a negatively charged chloride ion in the Ropivacaine molecule. It is a local anesthetic commonly used for pain relief and anesthesia during surgery.
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Ropivacaine hydrochloride is a local anesthetic often used for pain relief and anesthesia during surgery.
It belongs to a relatively new class of local anesthetics, a drug that blocks the conduction of nerve impulses. Its mechanism of action is to reduce the excitability by affecting the sodium ion channel of the neuronal membrane, increasing the potential of the neuronal membrane. Its action is limited to the local tissue and peripheral nervous system and does not affect the whole body, which makes it less side effects. Because it has less inhibitory effect on the cardiovascular system, it has higher safety in clinical application.
(1) Surgical pain relief:
The most common application of it is as a surgical analgesic. For example, it is used in obstetric procedures such as caesarean section and vaginal delivery, and other procedures such as gastrointestinal and urological procedures. It works by blocking the transmission of pain signals through the local injection anesthetic mechanism. It can also be administered topically to prolong pain relief after surgery.
(2) Nerve block:
It is also used for nerve blocks such as spinal and epidural blocks. These procedures require localized injections to the spinal cord or nerve roots to achieve sufficient anesthesia to achieve the desired effect. It is less toxic and has fewer side effects than other local anesthetics.
(3) Pain management:
It is also used to manage pain associated with diseases such as cancer pain. This drug is usually given in combination with other medicines to improve pain control.
(4) Local anesthesia:
In addition to its application in surgery, it can also be used as a local anesthetic in analgesic treatment. For example, in the field of dentistry, the drug can be injected locally to numb the area of the mouth to relieve pain in patients.
As a long-acting amide local anesthetic, it has shown significant advantages in the field of animal anesthesia due to its unique pharmacological properties, especially playing a key role in surgical anesthesia, postoperative analgesia, and special scenario applications.
Ropivacaine hydrochloride monohydrate reversibly inhibits the influx of sodium ions into nerve fibers, blocks pulse conduction, and acts as an inhibitor of K2P dual pore potassium channel TREK-1 (IC50 value of 402.7 μ M), further enhancing its anesthetic efficacy. Its left-handed structure (S-enantiomer) results in low lipid solubility, with a distribution rate of 141 at pH 7.4, which endows it with a "sensory motor blockade separation" effect. For example, in the experiment of rabbit vagus nerve specimens, the inhibitory effect of ropivacaine on motor fibers was 16% weaker than that of bupivacaine, while its inhibitory effect on sensory fibers was only 3% weaker. This difference is particularly important in animal anesthesia, as it can reduce postoperative movement disorders, promote early activity, and is particularly suitable for animal surgeries that require rapid recovery of motor function.
Diversified clinical application scenarios
1. Surgical anesthesia
Epidural anesthesia: Ropivacaine is the preferred medication for hip, gynecological, and lower limb surgeries in dogs, cats, and other animals. Research has shown that a concentration of 7.5mg/ml and a dose of 15-25ml can provide effective anesthesia for 3-5 hours, with mild motor block and fast postoperative recovery. For example, in hip replacement surgery in dogs, epidural anesthesia with ropivacaine can significantly reduce postoperative pain scores and lower the demand for opioid drugs.
Local infiltration anesthesia: 0.25% ropivacaine is used for wound infiltration after canine hernia repair surgery.
The analgesic effect is comparable to bupivacaine, but the motor block is lighter, which is beneficial for postoperative functional recovery. In addition, in ophthalmic surgery, a mixture of 2% lidocaine and 0.75% ropivacaine is injected, with an onset time of only 3 minutes and a maintenance time of over 5 hours, meeting surgical needs and achieving postoperative analgesia.
2. Postoperative analgesia management
Continuous epidural infusion: Ropivacaine significantly delays the development of neuropathic pain caused by peripheral nerve injury by prolonging the anti allodynia and anti allodynia time. For example, in postoperative analgesia in dogs, continuous epidural infusion of 0.2% ropivacaine at a rate of 6-10ml/h can provide effective analgesia, accompanied only by mild motor nerve block.
Multimodal analgesia: Combined with opioid drugs can reduce the dosage of local anesthetics and lower the risk of systemic toxicity. For example, in postoperative analgesia in cats, the combination of ropivacaine and low-dose fentanyl can prolong the analgesia time to more than 6 hours.
3. Special scenario applications
Superficial surgery: 0.375% ropivacaine is used for superficial lower limb surgery in dogs and cats, which can produce significant sensory motor separation and have minimal impact on the circulatory system. It is suitable for elderly or animals with cardiovascular dysfunction.
Neuropathic pain: Ropivacaine reduces the risk of pulmonary edema by inhibiting the increase in filtration coefficient caused by pressure, and inhibits NO production, thereby reducing hypertensive lung injury. For example, in the neuropathic pain model of dogs, ropivacaine can significantly alleviate mechanical hyperalgesia and thermal hyperalgesia.
Although ropivacaine is widely used in animal anesthesia, its spinal neurotoxicity remains controversial. For example, rat experiments have shown that continuous subarachnoid block with 1% ropivacaine can cause damage to the ultrastructure of spinal cord nerves. In addition, personalized doses will be developed to address metabolic differences among different species such as dogs, cats, and rabbits
The synthesis method of it is mainly divided into five steps:
Obtaining the chiral precursor Ropivacaine;
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Converting Ropivacaine hydrochloride into amino acids through a two-step reaction;
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Synthesizing amides by Mitsunobu reaction;
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Complete the construction of orthogonal alanine side chains by reduction and alkylation;
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Finally, synthesize Ropivacaine with the obtained amino acid and levovorican, and then react with hydrochloric acid to prepare it.
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Concrete steps Synthetic steps:
The first is the synthesis of the chiral precursor saccharone, which is an important intermediate for the preparation of Ropivacaine by cracking. The intermediate is generally synthesized from D-sorbose, including the following steps:
Step 1:
Carry out Claisen condensation of D-sorbose and L-maltose tautomers under acidic conditions to obtain 1,6-di-O-ethyl-D-sorbose molecule.
Step 2:
Epoxidation of this molecule gives the form of glycidone.
Step 3:
Reacting glycidone and benzylamine under the catalysis of p-toluenesulfonic acid to obtain the chiral precursor glucosone.
For the second step, saccharone must first be converted to the corresponding α-amino acid. This is accomplished in a two-step reaction:
The first step:
Using reducing amino acid decarboxylase to reduce the sugar ketone to the corresponding α-amino acid ester to obtain chiral proline (D-Pro) with natural amino acid configuration;
The second step:
Using the reaction system of pyridine/chloroform/propofol/diethylaminomercuric cyanide to convert D-Pro into the corresponding Boc-side chain protected nitrile acid to obtain N-Boc-D-Pro.
The chiral Boc-proline was reacted with 3-naphthoyl chloride and N-(2-propenyl)-p-toluenesulfonylimide (PPTS) by the Mitsunobu reaction to complete the construction of the amide bond and synthesize 3-carbethoxy-N -(2,6-dimethylphenyl)-2-(prop-2-en-1-yloxy)propanamide.
This step is to complete the construction of orthogonal alanine side chains by reduction and alkylation. Specific steps are as follows:
The first step:
Reduce 3-carbethoxy-N-(2,6-dimethylphenyl)-2-(prop-2-en-1-yloxy)propanamide, remove the carboxylic acid group, and obtain 3-amino-N-(2 ,6-dimethylphenyl)-2-propanol.
The second step:
Use the alkylation reaction to alkylate the ortho-position of 3-amino-N-(2,6-dimethylphenyl)-2-propanol to obtain 3-N-(2,6-dimethylphenyl)-2-( propylamino) propanol
Finally, it is synthesized by condensing 3-N-(2,6-dimethylphenyl)-2-(propylamino) propanol and levovorican to generate Ropivacaine. Subsequently, the obtained Ropivacaine was reacted with hydrochloric acid to prepare product.
In summary, the synthesis method of it is mainly divided into five steps, including the preparation of glycosone, the conversion of glycosone into amino acid, the synthesis of amide by Mitsunobu reaction, the reduction and alkylation to complete the orthogonal alanine The construction of the side chain and the final synthesis of Ropivacaine and preparation of product. This synthetic route has been proven to be a high-yield, high-purity method.
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Chemical Formula |
C17H26N2OCl |
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Exact Mass |
310 |
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Molecular Weight |
311 |
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m/z |
310 (100.0%), 311 (18.4%), 312 (32.0%), 313 |
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Elemental Analysis |
C, 65.68; H, 8.75; Cl, 11.40; N, 9.01; O, 5.15 |
Pharmacological mechanism of action:
The pharmacological mechanism of it mainly involves the following three aspects:
Sodium channel blockade:
It is a local anesthetic that produces anesthesia and pain relief by blocking sodium ion channels around nerve fibers. When it enters nerve fibers, it binds to sodium channels, reducing their activity. Since sodium ions are an essential component of nerve impulse transmission, blockade of this sodium channel reduces or completely prevents the conduction of nerve impulses, thereby producing anesthesia.
The role and selectivity of ion channels:
In general, it can selectively block different types of ion channels. Under loading conditions, the selectivity of sodium channels is significantly increased, so that when local anesthetic drugs enter cells and act on sodium channels, only sodium channels are affected, while calcium and potassium channels are not affected. This means that it is able to produce anesthesia by selectively blocking sodium channels without affecting calcium and potassium channels. This is due to its stronger affinity to sodium ion channels, ie higher receptor affinity.
Nutrient consumption of anesthetics:
Ropivacaine hydrochloride may also play a role in the nutrient consumption of the anesthetic. When anesthetics enter cells, they interact with metabolites inside the cells, consuming energy. According to research, lower concentrations and small doses of product do not affect energy metabolism, but high concentrations and large doses lead to cell death and increased energy expenditure.
FAQ
What is ropivacaine hcl used for?
A drug used to control pain and to cause a temporary loss of feeling in one part of the body, during and after surgery. It is also being studied for pain control after cancer surgery.
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