84057-95-4 Usage
Description
Ropivacaine is an aminoamide local anaesthetic drug commonly marketed by AstraZeneca under the trade name Naropin. Naropin was launched in 1996 in Australia, Denmark, Finland, the Netherlands and Sweden as a local anesthetic. It can be prepared in a number of ways the most efficient involves a three step sequence beginning with L-pipecolic acid. This compound is the first one in this family to be produced as the pure (S)- enantiomer. The (R)-enantiomer has been shown to have cardiotoxic effects. Thus ropivicaine has less cardiovascular and CNS toxicity than bupivacaine. It is a Na channel blocker that is specific for affecting nerve fibers responsible for transmission of pain (Aδ and C) with no effect on fibers responsible for motor function (Aβ). Clinically, it has distinct advantages over bupivacaine. Its effects are slower in onset, less intense and have a shorter duration. This is a result of extensive metabolism in the liver to the 3-hydroxy isomer by CYPIA2 isoenzyme.Ropivacaine is an anesthetic (numbing medicine) that blocks the nerve impulses that send pain signals to your brain.Ropivacaine is used as a local (in only one area) anesthesia for a spinal block, also called an epidural. The medication is used to provide anesthesia during a surgery or C-section, or to ease labor pains.https://www.drugs.com/mtm/ropivacaine.html
Uses
Different sources of media describe the Uses of 84057-95-4 differently. You can refer to the following data:
1. Ropivacaine is a pure S(-)-enantiomer of propivacaine. It is a long-acting amide local anesthetic that has efficacy and potency nearly as high as bupivacaine and levobupivacaine but has lower CNS and cvS toxicity. If there are any differences between bupivacaine and ropivacaine it is the slightly shorter period of activity in spinal and epidural applications and a lowered ability to penetrate large motor nerves. It is the reduced lipophilicity that contributed to the lowered penetration of the motor nerves, combined with its stereoselective properties that allows ropivacaine to have significantly reduced Cvs toxicity compared to bupivacaine (Simpson et al. 2005). Ropivacaine has a diphasic effect on peripheral vasculature-it is vasoconstrictive when injected at a concentration below 0.5 w/v% and there is dilation at concentrations over 1 w/v% (Cederholm et al. 1992).Ropivacaine HCl is an anaesthetic agent and blocks impulse conduction in nerve fibres through inhibiting sodium ion influx reversibly.http://www.selleckchem.com/products/ropivacaine-hcl.html
2. (S)-Ropivacaine acts as a local anaesthetic for use during medical procedures. Frequently used in epidural procedures as a labor analgesia
Definition
ChEBI: A piperidinecarboxamide-based amide-type local anaesthetic (amide caine) in which (S)-N-propylpipecolic acid and 2,6-dimethylaniline are combined to form the amide bond.
Brand name
Narapin [as hydrochloride] (Astra).
Biological Functions
Ropivacaine (Naropin) is a recently developed longacting
amide-linked local anesthetic. Its duration of action
is similar to that of bupivacaine, but it is slightly less
potent and requires higher concentrations to achieve the
same degree of block. Its primary advantage over bupivacaine
is its lesser degree of cardiotoxicity.
General Description
The recognized increase in cardiotoxicity of one bupivacaineisomer led to the stereospecific production of ropivacaine asthe single “S” (-) enantiomer. Ropivacaine is the propylanalog of mepivacaine (methyl) and bupivacaine (butyl). ThepKa of the tertiary nitrogen is 8.1, and it displays the same degreeof protein binding as bupivacaine ( 94%). Althoughropivacaine has similar properties as bupivacaine, it displaysless cardiotoxicity. The shortened alkyl chain gives it approximatelyone third of the lipid solubility of bupivacaine.
Mechanism of action
Ropivacaine is a member of the amino amide class of local anesthetics and is supplied as the pure S-(- )-enantiomer. Local anesthetics block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone.
Pharmacology
This is a single (S–) enantiomer, similar in structure to bupivacaine.
S ubstitution of a propyl for the butyl side chain of bupivacaine reduces lipid
solubility; this leads to reduced potential for toxicity and also greater
separation between sensory and motor blockade. Efficacy is similar, but
motor block is reduced compared with equianalgesic doses of racemic
bupivacaine.
Clinical Use
Ropivacaine is a long-acting amide-type local anestheticwith inherent vasoconstrictor activities, so it does not requirethe use of additional vasoconstrictors. It is approved forepidural, nerve block, infiltration, and intrathecal anesthesia.
Side effects
Reactions to ropivacaine are characteristic of those associated with other amide-type local anesthetics. A major cause of adverse reactions to this group of drugs may be associated with excessive plasma levels, which may be due to overdosage, unintentional intravascular injection or slow metabolic degradation.Check with your doctor or nurse immediately if any of the following side effects occur:More commonBlurred visionchest pain or discomfortconfusiondizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting positionlightheadedness, dizziness, or faintingslow or irregular heartbeatsweatingunusual tiredness or weaknessLess commonBurning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelingschillsdecrease in frequency or amount of urinedifficulty in passing urine (dribbling)feverpainful urinationRareAbsence of or decrease in body movementagitationanxietyhttps://www.mayoclinic.org/drugs-supplements/ropivacaine-injection-route/side-effects/drg-20065875https://www.accessdata.fda.gov/
Metabolism
The metabolism of ropivacaine in human is mediated by hepatic CYP1A2 isozymes and, to a minor extent, by CYP3A4. The major metabolite is 3-hydroxyropivacaine, and the minor metabolite is (S)-2′,6′-pipecoloxylidide (a N-dealkylated product).Ropivacaine is extensively metabolized in the liver, predominantly by aromatic hydroxylation mediated by cytochrome P4501A to 3-hydroxyropivacaine. After a single IV dose approximately 37% of the total dose is excreted in the urine as both free and conjugated 3-hydroxy ropivacaine. Low concentrations of 3-hydroxy ropivacaine have been found in the plasma. Urinary excretion of the 4-hydroxy ropivacaine, and both the 3-hydroxy N-de-alkylated (3-OH-PPX) and 4-hydroxy N-dealkylated (4-OH-PPX) metabolites account for less than 3% of the dose. An additional metabolite, 2- hydroxy-methyl-ropivacaine, has been identified but not quantified in the urine. The N-de-alkylated metabolite of ropivacaine (PPX) and 3-OH-ropivacaine are the major metabolites excreted in the urine during epidural infusion. Total PPX concentration in the plasma was about half as that of total ropivacaine; however, mean unbound concentrations of PPX were about 7 to 9 times higher than that of unbound ropivacaine following continuous epidural infusion up to 72 hours. Unbound PPX, 3- hydroxy and 4-hydroxy ropivacaine, have a pharmacological activity in animal models less than that of ropivacaine. There is no evidence of in vivo racemization in urine of ropivacaine.https://www.accessdata.fda.gov
Check Digit Verification of cas no
The CAS Registry Mumber 84057-95-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,4,0,5 and 7 respectively; the second part has 2 digits, 9 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 84057-95:
(7*8)+(6*4)+(5*0)+(4*5)+(3*7)+(2*9)+(1*5)=144
144 % 10 = 4
So 84057-95-4 is a valid CAS Registry Number.
InChI:InChI=1/C17H26N2O.CH4O3S/c1-4-11-19-12-6-5-10-15(19)17(20)18-16-13(2)8-7-9-14(16)3;1-5(2,3)4/h7-9,15H,4-6,10-12H2,1-3H3,(H,18,20);1H3,(H,2,3,4)
84057-95-4Relevant articles and documents
Determination of the enantiomeric purity of S-ropivacaine by capillary electrophoresis with methyl-β-cyclodextrin as chiral selector using conventional and complete filling techniques
Amini, Ahmad,Wiersma, Britta,Westerlund, Douglas,Paulsen-Soerman, Ulla
, p. 17 - 24 (1999)
Capillary electrophoresis (CE) methods based on the conventional and complete filling techniques for determination of the enantiomeric purity of S-ropivacaine are described. The complete filling technique is a separation method which can be used instead of the partial filling technique in order to reduce the total analysis time, when the chiral selector solution does not absorb UV light. In the complete filling technique the total length of the capillary is filled with the chiral selector solution, prior to application of the analyte. During the run both ends of the capillary are connected to the background electrolyte, i.e. without chiral agent. An interlaboratory study was performed to validate the method. The limit of detection and quantification for R-ropivacaine were found to be about 0.6 and 1.6 μg/ml, respectively, corresponding to 0.1 and 0.25% enantiomeric purity of S-ropivacaine. Good performances were demonstrated for the repeatability and linearity. The consumption of the chiral selector was about 160 times lower with the complete filling technique compared with the conventional CE technique. Copyright (C) 1999 Elsevier Science B.V.
A convenient and highly enantioselective synthesis of (S)-2-pipecolic acid: an efficient access to caine anesthetics
Yang, Yuyan,Li, Hua,You, Zhonglin,Zhang, Xingxian
, p. 3084 - 3089 (2021/08/12)
A novel and enantioselective synthesis of (S)-2-pipecolic acid (5) has been achieved from Oppolzer’s sultam (1) and ethyl N-(diphenylmethylene)glycinate (2) as readily available starting materials. The highly stereoselective alkylation of chiral glycine intermediate (3) with 1,4-dibromobutane afforded the key backbone of (S)-2-pipecolic acid (5) in one-step that was utilized into the preparation of the local anesthetics mepivacaine, ropivacaine and bupivacaine.
Effect of Partially Fluorinated N-Alkyl-Substituted Piperidine-2-carboxamides on Pharmacologically Relevant Properties
Vorberg, Raffael,Trapp, Nils,Zimmerli, Daniel,Wagner, Bj?rn,Fischer, Holger,Kratochwil, Nicole A.,Kansy, Manfred,Carreira, Erick M.,Müller, Klaus
, p. 2216 - 2239 (2016/10/19)
The modulation of pharmacologically relevant properties of N-alkyl-piperidine-2-carboxamides was studied by selective introduction of 1–3 fluorine atoms into the n-propyl and n-butyl side chains of the local anesthetics ropivacaine and levobupivacaine. The basicity modulation by nearby fluorine substituents is essentially additive and exhibits an exponential attenuation as a function of topological distance between fluorine and the basic center. The intrinsic lipophilicity of the neutral piperidine derivatives displays the characteristic response noted for partially fluorinated alkyl groups attached to neutral heteroaryl systems. However, basicity decrease by nearby fluorine substituents affects lipophilicities at neutral pH, so that all partially fluorinated derivatives are of similar or higher lipophilicity than their non-fluorinated parents. Aqueous solubilities were found to correlate inversely with lipophilicity with a significant contribution from crystal packing energies, as indicated by variations in melting point temperatures. All fluorinated derivatives were found to be somewhat more readily oxidized in human liver microsomes, the rates of degradation correlating with increasing lipophilicity. Because the piperidine-2-carboxamide core is chiral, pairs with enantiomeric N-alkyl groups are diastereomeric. While little response to such stereoisomerism was observed for basicity or lipophilicity, more pronounced variations were observed for melting point temperatures and oxidative degradation.
This product is a nationally controlled contraband, and the Lookchem platform doesn't provide relevant sales information.