Local Anesthetic Activity Research Articles

Motor and sensory blocking effect of intrathecal fentanyl versus dexmedetomidine as adjuvants to bupivacaine for cesarean section

Background Intrathecal α2 agonists prolong the duration of action of local anesthetics and reduce the required dose. Dexmedetomidine is an α2 receptor agonist, and its α2/α1 selectivity is eight times higher than that of clonidine. Aim The aim of this study was to determine the effect of adding dexmedetomidine and fentanyl to intrathecal bupivacaine on the onset time and duration and intensity of motor and sensory blocks for cesarean section. Patients and methods The study was carried out on 40 adult female patients who were randomly classified using closed envelope method into two equal groups, with 20 patients in each: group D patients received intrathecally 2.5 ml volume of 10 mg (2 ml) 0.5% hyperbaric bupivacaine and 10 µg dexmedetomidine in 0.5 ml (prepared by diluting 1 ml dexmedetomidine in 5 ml of normal saline), and group F patients received intrathecally 2.5 ml volume of 10 mg (2 ml) 0.5% hyperbaric bupivacaine and 20 µg fentanyl in 0.5 ml (prepared by diluting 2 ml fentanyl in 2.5 ml of normal saline). The aim was to evaluate motor and sensory block. Sensory block assessment: the onset and duration of sensory block was assessed by ice cube method, and time taken from intrathecal injection to the highest level of sensory block and sensory regression to the L1 dermatome were recorded. On achieving T7 sensory blockade level, surgery was allowed. Motor block assessment: onset and degree of motor block was assessed by Bromage scale: 0, no paralysis; 1, inability to raise extended leg; 2, inability to flex the knee; and 3, inability to flex the ankle (complete motor block). Results Sensory and motor block onset times were shorter in group D than in group F. The regression of the sensory block to S1 dermatome and Bromage 0 were longer in group D than group F. The two-dermatome regression time was longer in group D than group F. There was a statistically significant decrease in group F regarding systolic, diastolic, and mean arterial blood pressures and heart rate than group D. There was no statistically significant difference among the two groups regarding arterial oxygen saturation and respiratory rate. Neonatal outcome was normal in all groups. Conclusion Intrathecal dexmedetomidine addition to bupivacaine for spinal anesthesia synergistically increases block duration and shortens sensory and motor block onset time without any significant adverse effects.

Synthesis, Characterization and Assessment of Local Anesthetic Activity of Some Benzohydroxamic Acids

Synthesis, Characterization and Assessment of Local Anesthetic Activity of Some Benzohydroxamic Acids

Local anesthetics induce interdigitation and thermotropic changes in dipalmitoylphosphatidylcholine bilayers

The molecular mechanism underlying the action of local anesthetics is still elusive. Phenylethanol (PEtOH) is an ingredient of essential oils with a rose-like odor and has been used as a local anesthetic. In this work, we have explored the effect of PEtOH on thermotropic behavior and organization of dipalmitoylphosphatidylcholine (DPPC) membranes utilizing differential scanning calorimetry (DSC) and small angle X-ray scattering (SAXS). Our results indicate that the phase transition temperature of DPPC exhibited decrease with increasing PEtOH concentration. This is accompanied by hysteresis (difference in phase transition between the heating and cooling scans). We defined the threshold concentration of PEtOH as the concentration at which the difference in phase transition temperature between the heating and cooling thermograms is maximum. Interestingly, changes in enthalpy, entropy, and full width at half maximum displayed biphasic behavior beyond the threshold concentration of PEtOH. The biphasic change in thermodynamic parameters corresponding to phase transtition, coupled with hysteresis, is indicative of interdigitation in DPPC bilayers. We confirmed this proposition by SAXS measurements which show formation of the interdigitated phase in DPPC bilayers at and above the threshold concentration of PEtOH. To the best of our knowledge, these results constitute the first report describing the interdigitation of membrane bilayers induced by PEtOH. We further show that the formation of interdigitated phase in DPPC bilayers depends on PEtOH concentration and temperature. Our results could be useful in ongoing efforts to address the mechanism of action of local anesthetics in model and biological membranes.

Synthesis, biological evaluation, and molecular docking of ropivacaine analogs as local anesthetic agents

Two series of ropivacaine analogs (4a–4q, 7a–7c) were synthesized, and their biological activities were evaluated as local anesthetic agents. Most of the compounds displayed detectable local anesthetic characteristics. Among them, compound 4l showed significant efficacy with sciatic nerve block, infiltration, corneal surface, and spinal anesthetic activities. It was as potent as the reference compound ropivacaine. Dissociation constants of these compounds were 5.9–7.9. In addition, molecular docking modeling on compound 4l and ropivacaine was performed to delineate structural requirements and potential mechanisms for the local anesthetic activity. This study provides valuable new information for our ongoing endeavor to design more potent local anesthetics.

Local Anesthetic Drug Inhibits Growth and Survival in Chronic Myeloid Leukemia Through Suppressing PI3K/Akt/mTOR

BackgroundApart from the known anesthetic and antiarrhythmic effects, recent studies also highlight the anticancer activities of local anesthetics. In line with the findings, our work shows that ropivacaine, an amide-linked local anesthetic drug, targets chronic myeloid leukemia (CML) via inhibiting PI3K/Akt/mTOR. Materials and MethodsThe effects of ropivacaine in CML cell lines and primary stem or progenitor cells were investigated using apoptosis, proliferation and colony formation assays. The effects of ropivacaine on proliferation and survival pathways were analyzed using Western blot. ResultsWe demonstrate that ropivacaine dose and time dependently inhibits proliferation in CML cell lines via arresting cell at G2/M stage. Ropivacaine induces apoptosis in CML cells. In addition, the anti-CML activity of ropivacaine is mainly through growth arrest rather than apoptosis induction. We further demonstrate that ropivacaine induces apoptosis and inhibits colony formation in CD34 progenitor or stem cells derived from patients with blast phase-CML. Importantly, combination of ropivacaine with imatinib or dasatinib (Bcr-Abl tyrosine kinase inhibitors) is significantly more effective in targeting CML cell lines as well as blast phase-CML CD34 cells than imatinib or dasatinib alone. We further demonstrate that ropivacaine inhibits phosphorylation of essential molecules involved in PI3K/Akt/mTOR signaling pathways in CML cells. Akt overexpression significantly reverses the effects of ropivacaine, further confirming that ropivacaine acts on CML cells via inhibition of PI3K/Akt/mTOR. ConclusionsOur work provide rationales on clinical trials for the use of local anesthetics in CML by demonstrating the anti-CML effects of ropivacaine and the molecular mechanism of its action.

Search Of High Active And Low Toxic Newly Synthesized Derivatives Of Piperidine For Regional Anesthesia

comparative assessment of local anesthetic activity of newly synthesized derivatives of piperidine for regional anesthesia, depending on their chemical structure. local anesthesia was determined by the method of “tail-flick” on white rats. For research of activity of the compound at the particular type of anesthesia the great important index is duration of complete anesthesia. The duration of complete anaesthesia of LAS-174 was similar to trimecaine, slightly higher than that of novocaine and a little bit less than lidocaine (p>0.05). Total duration of action of LAS-174 is higher than the novocaine and trimekain, and a few exceeding that of lidocaine (p>0.05). LAS-175 index of full anesthesia was 2 times higher than trimekain, 2.5 times than novocaine and a few more than lidocaine (p>0.05). By the total duration this compound exceeds the matched values of trimethoprim, lidocaine and novocaine in 3.4, 1.9 and 4.6 times, respectively. Replacement of the propyl radical to Amillic in the side chain at the 4-th carbon atom of the piperidine ring enhances local activity by the similar toxicity. In 1% solution duration of anesthesia of LAS-190 is similar to the trimecaine and slightly lower than the lidocaine. LAS-189 shows a weaker effect than trimekain and lidocaine (p>0.05). LAS-189 and 190 by the duration of anesthesia was more effective than novocaine, but this difference is not statistically significant. Replacement of the propyl radical (LAS-189) to the phenyl (LAS-190) contributes to increase of local anesthetic activity, especially for the total duration. Acute toxicity of LAS-189 is 750±of 35.56, LAS-190 - 1284±43,87. the Introduction of a cyclopropane radical at the triple bind of the piperidine ring leads to increased local anesthetic effect, weighting of the radical at the 4th carbon atom contributes to the growth of activity and lower toxicity.

Polypharmacology of Aconitum and Delphinium sp. Diterpene Alka loids: Antiarrhythmic, Analgesic and Anti-Inflammatory Effects

Up to now, the polypharmacology of diterpene alkaloids isolated from Aconitum and Delphinium sp. has been extensively studied. From 1998 to 2014, more than 400 new diterpene alkaloids were isolated from Nature. Pharmacological researches have indicated that many diterpenoid alkaloids are the main bioactive components which have arrhythmogenic, local anesthetic, antiarrhythmic, curariform, analgesic, hypotensive, anti-inflammatory, anti-microbial, anti-tumor, spasmolytic, neurotropic and psychotropic activities. In the present review, the antiarrhythmic, analgesic and anti-inflammatory activities of diterpene alkaloids as well as the pharmacological mechanisms were summarized. Moreover, their Structure-Activity Relationship was also analyzed. Keywords: Diterpene alkaloids, Aconitum, Delphinium sp., antiarrhythmic activity, analgesic activity, anti-inflammatory activity.

The Role Of Epidural Fentanyl In Painless Labour

Background: Epidural analgesia for providing Painless normal vaginal deliveries has been developed over the last 20 years,epidural local anaesthetics was the only available option. However, cetain drugs were added with the local anaesthetics to improves the quality of analgesia.Aims : to ascertain the efficiency of fentanyl added to the epidural local anaesthetics in comparison with the use of an epidural local anaesthetics alone.Patient and methods : This study was carried out on 30 parturients prepared for painless normal vaginal delivery under epidural analgesia in Al-khuder general hospital.
 Anaesthesiologist (ASA) classification were grade 1 between 20-40 of age with length taller than 160 cm.Subjects were allocated into two groups (15 patients in each group): Group A (n=15) received through an epidural catheter 8 ml lidocaine 0.75%+ 2ml normal saline for the first main dose and subsequent top up doses. Group B (n=15) received through an epidural catheter 8ml lidocaine o.75% + 20 microgram fentanyl diluted with normal saline to a total 2 ml volume for the first main dose and subsequent top up doses. Onset of action of local anaesthetic , the interval from initial bolus dose to the maternal request for additional analgesia , the number of top up doses and the neonatal condition in both groups were recorded.Results : the group B is associated with shorter onset of action , longer interval from initial bolus dose to the maternal request for additional dose and a lesser number of top up doses than group A. The effect on neonatal condition manifested by APGAR score at 5 minute after delivery is similar in both groups.conclusions : 20 microgram of fentanyl added to the usual dose of local anaesthetic epidurally is safe , effective and much better than the use of epidural local anaesthetic alone.

Optimised NLC: a nanotechnological approach to improve the anaesthetic effect of bupivacaine

The short time of action and systemic toxicity of local anaesthetics limit their clinical application. Bupivacaine is the most frequently used local anaesthetic in surgical procedures worldwide. The discovery that its S(−) enantiomeric form is less toxic than the R(+) form led to the introduction of products with enantiomeric excess (S75:R25 bupivacaine) in the market. Nevertheless, the time of action of bupivacaine is still short; to overcome that, bupivacaine S75:R25 (BVCS75) was encapsulated in nanostructured lipid carriers (NLC). In this work, we present the development of the formulation using chemometric tools of experimental design to study the formulation factors and Raman mapping associated with Classical Least Squares (CLS) to study the miscibility of the solid and the liquid lipids. The selected formulation of the nanostructured lipid carrier containing bupivacaine S75:R25 (NLCBVC) was observed to be stable for 12 months under room conditions regarding particle size, polydispersion, Zeta potential and encapsulation efficiency. The characterisation by DSC, XDR and TEM confirmed the encapsulation of BVCS75 in the lipid matrix, with no changes in the structure of the nanoparticles. The in vivo analgesic effect elicited by NLCBVC was twice that of free BVCS75. Besides improving the time of action, no statistical difference in the blockage of the sciatic nerve of rats was found between 0.125% NLCBVC and 0.5% free BVCS75. Therefore, the formulation allows a reduction in the required anaesthesia dose, decreasing the systemic toxicity of bupivacaine, and opening up new possibilities for different clinical applications.

Combined Approach of QSAR and Docking Studies for the Design of Local Anaesthetic Agents

Heterocyclic scaffold, benzotriazole and its derivatives are potential anaesthetic agents that act locally. QSAR and docking analysis of previously synthesized benzotriazolyl derivatives were modelled for their local anaesthetic action using computer assisted multiple regression analysis. It provides the insight about the structural requirements for the local anaesthetic action. A training set comprising of 16 molecules and test set of 8 molecules were selected for present investigation by using sphere exclusion method with dissimilarity value of +4.0. The validation of the QSAR models was performed by cross-validation and external test set prediction. Docking studies was performed using GRIP docking methodology. Further GRIP docking with the pentameric ligand gated ion channel, 2XQ3 facilitated the mechanistic analysis of interactions of the test molecules active site residues.

AaPDR3, a PDR Transporter 3, Is Involved in Sesquiterpene β-Caryophyllene Transport in Artemisia annua.

Artemisinin, a sesquiterpenoid endoperoxide, isolated from the plant Artemisia annua L., is widely used in the treatment of malaria. Another sesquiterpenoid, β-caryophyllene having antibiotic, antioxidant, anticarcinogenic and local anesthetic activities, is also presented in A. annua. The role played by sesquiterpene transporters in trichomes and accumulation of these metabolites is poorly understood in A. annua and in trichomes of other plant species. We identified AaPDR3, encoding a pleiotropic drug resistance (PDR) transporter located to the plasma membrane from A. annua. Expression of AaPDR3 is tissue-specifically and developmentally regulated in A. annua. GUS activity is primarily restricted to T-shaped trichomes of old leaves and roots of transgenic A. annua plants expressing proAaPDR3: GUS. The level of β-caryophyllene was decreased in transgenic A. annua plants expressing AaPDR3-RNAi while transgenic A. annua plants expressing increased levels of AaPDR3 accumulated higher levels of β-caryophyllene. When AaPDR3 was expressed in transformed yeast, yeasts expressing AaPDR3 accumulated more β-caryophyllene, rather than germacrene D and β-farnesene, compared to the non-expressing control.

Improvement of cytotoxic activity of local anesthetics against human breast cancer cell line through the cyclodextrin complexes

ABSTRACTAmong the potent anticancer agents, Local Anesthetics (LA) have been found to be efficient against many different types of cancer cells. However, the major disadvantage associated with the use of LA its low systemic bioavailability when administered due to its poor aqueous solubility. Our present work concentrates on improving the bio-availability by complexing with cyclodextrin. We synthesized the inclusion complexion by co-precipitation method which is an efficient method among other and characterized the formulation of complex by UV and fluorescence studies. The in-vitro study of cytotoxicity against breast cancer cell line is performed. Our study shows the formation of the complex with 1:1 ratio and the result show both Benzocaine and Tetracaine inclusion complex has higher potential towards breast cancer cell than the free drug.

Anesthetics mechanism on a DMPC lipid membrane model: Insights from molecular dynamics simulations

To provide insight into the molecular mechanisms of local anesthetic action, we have carried out an extensive investigation of two amide type local anesthetics, lidocaine and articaine in both charged and uncharged forms, interacting with DMPC lipid membrane. We have applied both standard molecular dynamics simulations and metadynamics simulations to provide a detailed description of the free energy landscape of anesthetics embedded in the lipid bilayer. The global minimum of the free energy surface (equilibrium position of anesthetics in the lipid membrane) occurred around 1nm of the bilayer center. The uncharged anesthetics show more affinity to bind to this region compared to the charged drugs. The binding free energy of uncharged lidocaine in the membrane (−30.3kJ/mol) is higher than uncharged articaine (−24.0kJ/mol), which is in good agreement with higher lipid solubility of lidocaine relative to the articaine. The octanol/water partition coefficient of uncharged drugs was also investigated using expanded ensemble simulations. In addition, complementary standard MD simulations were carried out to study the partitioning behavior of multiple anesthetics inside the lipid bilayer. The results obtained here are in line with previously reported simulations and suggest that the different forms of anesthetics induce different structural modifications in the lipid bilayer, which can provide new insights into their complex membrane translocation phenomena.

Antimicrobial Activity of Lidocaine, Bupivacaine, Mepivacaine and Ropivacaine on Staphylococcus epidermidis, Staphylococcus aureus and Bacillus subtilis

Introduction: Various studies have shown a possible antimicrobial activity of different local anaesthetics, which may affect the results of microbial assessment of biopsies. The purpose of this study was to test the antimicrobial activity of different commonly used anaesthetic agents on Staphylococcus epidermidis, Staphylococcus aureus and Bacillus subtitles to reproduce data and to compare the findings. Methods: Local anaesthetics tested were commercially available solutions of lidocaine (Xyloneural®, Xylanaest pur.®), bupivacaine (Bucain®), mepivacaine (Mecain®) and ropivacaine (Naropin®, Ropinaest®).2%, 1%, 0.5%, 0.25% and 0.1% (20, 10, 5, 2.5, 1 mg/ml) dilutions of these local anaesthetics were prepared with sterile 0.9% saline. Bacteria used in this study were Staphylococcus epidermidis, Staphylococcus aureus and Bacillus subtilis. 10 μl of different local anaesthetic dilution placed on thin wafers were added to Mueller Hinton Agar and cultured. After 24 hours, a zone of inhibition around the wafers was evaluated. Results: Local anaesthetics in different concentrations did not show any zone of inhibition on Staphylococcus epidermidis, Staphylococcus aureus or Bacillus subtilis. Conclusion: In summary, neither lidocaine, bupivacaine, mepivacaine nor ropivacaine showed an antibacterial effect on Staphylococcus epidermidis, Staphylococcus aureus and Bacillus subtilis. Implications: Due to these findings this local anaesthetics can be used in daily clinical routine to perform pain free diagnostic procedures in which culture specimens are to be obtained. Due to inconsistent results in prior studies, we recommend to use the lowest concentration possible of the local anaesthetic, also to avoid other possible side effects of local agents.

Autologous Conditioned Plasma Versus Placebo Injection Therapy in Lateral Epicondylitis of the Elbow: A Double Blind, Randomized Study.

Introduction There are various therapeutic approaches to the treatment of lateral epicondylitis, a highly prevalent musculoskeletal disorder. Recently, injection therapy with autologous conditioned plasma (ACP) has shown promise as a new approach. Methods Set up as a prospective, double-blind, randomized controlled clinical trial, this study involved 50 patients with lateral epicondylitis. Following external randomization, 25 patients received one round of injection therapy with ACP (platelet rich plasma, PRP), while the remaining 25 patients received a placebo of 0.9 % NaCl. All patients were re-evaluated with respect to lateral epicondylitis of the elbow at four-weeks and six-months post-injection. Results Out of 50 patients, 36 qualified for reevaluation, 18 patients from the ACP therapy group and 18 from the placebo group. The initial Disability of the Arm, Shoulder and Hand (DASH) score for all reevaluated patients was 36.4 in the ACP group, and 41.0 in the placebo group; both groups exhibited decreased DASH scores at the four-week and six-month post-injection follow-up (6 months: ACP 30.1, placebo 25.8). The decrease of the DASH score after 4 weeks was greater and qualified as statistically significant in the placebo group (p = 0.041), compared to the DASH score decrease in the ACP treatment group, which was statistically non-significant. Additionally, the difference between the DASH scores of the treatment and placebo groups was statistically non-significant four weeks and six months after treatment. Discussion The results of this study suggest a therapeutic effect inboth the ACP and placebo groups, with no evidence for a therapeutically significant difference between ACP and placebo treatments. It is hypothesized that, in accordance with the study protocols, injection with a local anaesthetic prior to ACP therapy may have an influence on the therapeutic effect of ACP. Future studies have to confirm recent findings that demonstrated a minimizing, or even inhibiting, action of local anaesthetics on the effects of ACP/PRP. Conclusion The effect of ACP/PRP injections needs to be investigated in future studies under standardized conditions.

Chromatographic Fingerprinting Analysis of Secondary Metabolites Present in Ethanolic Extract of Tabernaemontana divaricata (L.) R. Br. by HPTLC Technique

Tabernaemontana divaricata (L.) R. Br is a medicinal plant which is blongs to the family of Apocyanaceae, the whole plant extract possess many biological activities such as antioxidant activity, antiinflammatory activity and it has a very good local anesthetic and anti cancer activity. Therefore, the present study is an attempt to evaluate the present of secondary metabolites from ethanolic extract of Tabernaemontana divaricata (L.) using HPTLC analysis which was carried out to find the alkaloids, flavonoids, glycosides, poly phenols, steroids and tannins. In the results, the selected secondary metabolites were present in the ethanolic extract of T. divaricata (L.). Based on the results, this study can be concluded that this plant has variety of biological activities may be presence of alkaloids, flavonoids, glycosides, poly phenols, steroids and tannins in it. In future by isolating and identifying these compounds may be formulated to treat the various diseases.

Comparative evaluation of the local anesthetic activity of root extract of Anacyclus pyrethrum and its interaction at the site of injection in guinea pigs

Aim:The aim of the study was to evaluate the local anesthetic activity of root extracts of the Anacyclus pyrethrum, and to check its effect of interaction at the site of injection in guinea pigs.Materials and Methods:The study sample included thirty guinea pigs each weighing 450–500 g, maintained under standard conditions. The root extracts were prepared using three solvents, in 1% and 2% concentration and injected in guinea pigs. The animals were divided into five groups, six in each group based on the type of extract used along with a control and a standard drug. All the animals received 0.5 ml of intradermal injection of the prepared extract, with 1% concentration in the left and 2% in the right dorsal flank of the animal and were checked for local anesthetic activity by a pinprick test. After 72 h, biopsy was done from the injected site to check for drug interaction.Results:The number of negative response obtained from 2% ethanol extract is more effective when compared to other extracts. Histological samples showed inflammatory changes in 1% aqueous extract in a single animal.Conclusion:Among the test compounds, 2% ethanol showed more significant effect; hence, it is suggested to synthesize more compounds in this series and evaluate their pharmacological actions.

Evaluation of midazolam as an adjuvant to bupivacaine in supraclavicular brachial plexus block

Background The duration of the supraclavicular brachial plexus block is limited by the duration of action of local anesthetic used for the block. Many adjuvants are used to prolong the duration of the block. Few studies were carried on evaluate the effects of using midazolam as an adjuvant to bupivacaine in supraclavicular brachial plexus block. Aim The aim of the study was to evaluate the anesthetic characteristics of adding midazolam to bupivacaine during ultrasound-guided supraclavicular brachial plexus block. Patients and methods The study was carried out on 96 patients scheduled for upper limb surgeries. They were divided into three equal groups to receive ultrasound-guided supraclavicular brachial plexus block using 30 ml bupivacaine 0.5% in group I, 30 ml bupivacaine 0.5% and 30 µg/kg midazolam in group II, and 30 ml bupivacaine 0.5% in addition to 30 µg/kg intravenous midazolam in group III. Results The onset of sensory and motor block were significantly faster, and the durations were significantly longer in group II compared with groups I and III; furthermore, postoperative analgesia was significantly prolonged in group II (P Conclusion Midazolam is a valuable adjuvant to bupivacaine during ultrasound-guided supraclavicular brachial plexus block, which requires further evaluation.

Programmed intermittent epidural bolus improves efficacy of patient controlled epidural analgesia in postoperative pain management

Background: Postoperative acute pain will have negative impacts if not handled properly so it must be treated effectively. Patient Controlled Epidural Analgesia (PCEA) allows the patient to have an active role in determining the need of analgesia personally. Programmed Intermittent Epidural Bolus (PIEB) is a new method which proven better than Continuous Epidural Infusion. Ropivacaine has similar characteristic to Bupivacaine but with minimal cardiotoxic effect. Fentanyl as an adjuvant can accelerate the onset of action of local anesthetics in epidural analgesia. The purpose of this study was to compare the efficacy of PCEA+PIEB with PCEA as a modality of postoperative analgesia. Methods: Total 54 patients undergoing major surgery of the abdomen and lower extremities were divided into 2 groups randomly: PIEB+PCEA and PCEA. Then we did an evaluation of VAS, PCA demand, and total consumption of solution Ropivacaine 0.1% + Fentanyl 2 mcg/mL at 4 hours, 8 hours, and 24 hours postoperative Results: VAS at resting and at moving in both groups were found clinically comparable, although statistically, VAS at moving at 4 hours and 24 hours postoperative were lower in PCEA+PIEB group (p < 0.01). PCA attempted and PCA given were lower in PCEA+PIEB group (p = 0.05). Total consumption of solution until 8 hours postoperative was comparable in both groups but at 24 hours postoperative it was much greater in PCEA+PIEB group (p < 0.01). Conclusions: PCEA+PIEB have greater efficacy than PCEA. VAS (at resting and at moving), PCA attempted, and PCA given were lower in PCEA+PIEB group. Total consumption of solution Ropivacaine-Fentanyl until 8 hours postoperative was comparable, but at 24 hours postoperative it was much greater in PCEA+PIEB group. In orthopedic surgery, VAS at resting was obtained below 30 mm in PCEA+PIEB group but VAS at moving was obtained in the category of moderate pain in both groups.

4-(2-chloroacetamido) Benzoic Acid Derivatives as Local Anesthetic Agents: Design, Synthesis, and Characterization

Local anesthetic activity was investigated with an assumed hypothesis that the essential alkyl substituted nitrogen having strong ionization characteristics (pKa in basic side) generally found in local anesthetics can be replaced by amide nitrogen, having chloro methyl group attached to the carbonyl carbon of amide. In this type of arrangement, the inductive effect exerted by chlorine provided enough ionization character to amide nitrogen. Eight esters, ten amides and one imidazole derivatives of 4-(2-chloroacetamido) benzoic acid were synthesized by Fischer’s esterification, Schotten-Baumann and substitution reactions. The synthesized derivatives (A1–A18 and A.im) were characterized by various instrumental techniques.ACD Lab Suite® was used to determine various physiochemical properties of synthesized molecules. Initially, infiltration local anesthetic activity was determined by Bianchi’s method. Five compounds (A1, A2, A4, A10, and A.im) showed promising local anesthetic activity, where the comparison was made with lignocaine HCl, thus conforming assumed hypothesis. However, the studied compounds have potency lower than that of lignocaine HCl. Compounds showing promising activity with low toxicity were studied further by in-vivo rat sciatic nerve block method using increasing doses. A.im was studied for topological similarity with lignocaine HCl where it showed good local anesthetic activity and was relatively very less toxicity. The reduced toxicity of these molecules may be attributed due to the carbonyl chloro methyl side chain. Further structural advancement may be done by researchers to increase the potency of these compounds since they are relatively less toxic than lignocaine.