Binding effects of Alpinia galanga oil and its nanoemulsion 1 to GABAA receptors in rat cortical membranes

Anesthetic activity of Alpinia galanga oil (AGO) has been reported however the mechanism of action in mammals has not been clear. In the present study, the binding effects of AGO and its three active components to gamma-aminobutyric acid type A (GABAA) receptor in cortical membranes of Sprague-Dawley rats were firstly investigated using a [3H]muscimol binding assay. Dimethyl sulfoxide (DMSO) was used to deliver these test samples. The results showed that only AGO and methyl eugenol displayed positive modulation at the highest concentration whereas 1,8-cineole and 4-allylphenyl acetate were inactive. An oil-in-water nanoemulsion containing 20%w/w AGO (NE-AGO) was formulated to deliver AGO instead of DMSO. This NE-AGO significantly enhanced a specific [3H]muscimol binding to 179% of the control with EC50 of 391 µg/mL. The result correlates well to the amount of methyl eugenol in AGO. This result confirms that the anesthetic activity of AGO and methyl eugenol is associated with GABAA receptor modulation, while that of 1,8-cineole and 4-allylphenyl acetate is not and may instead be related to other mechanisms. AGO showed well-tolerated by human cells. Therefore, the formulated NE-AGO might be a promising alternative anesthetic product for humans.

Cerebral Sinus Thrombosis with Coexisting Secondary Hypoparathyroidism: Case Report for Clinical Education

Pethidine was the first synthetic opioid to be used to provide analgesia in humans and was shown also to have local anesthetic activity comparable with that of cocaine. The neonatal Apgar score after birth is an important factors of mortality of the newborn. In this regard, the type of drug used for the cesarean section is very important in the Apgar score of the cesarean section. Pethidine is an intermediate lipid-soluble opioid with both a postoperative analgesic mechanism and a sensory block which is known as the only opioid which can be used alone in the cesarean section under spinal anesthesia. We used pethidine as an alternative to bupivacaine in patients going under cesarean section.

Synthesis of procaine analogues containing pentafluoroethoxy groups in the aromatic nucleus

In order to synthesize procaine analogs containing one or two pentafluoroethoxy groups, a method for the synthesis of benzoic acids containing a pentafluoroethoxy group in the ortho-position of the benzene nucleus has been developed. An effective method for the synthesis of procaine structural analogues containing one or two pentafluoroethoxy groups has been proposed. It has been shown that the replacement of the amino group by the pentafluoroethoxy group in the procaine molecule leads to a significant increase in the local anesthetic activity of the obtained compounds. The most active compound was a structural analogue of procainamide containing two pentafluoroethoxy groups in positions 2 and 4. The formation of fluorine-containing analogues of procaine was confirmed by 1H, 19F and 13C NMR spectroscopy and mass spectrometry.

SYNTHESIS, STRUCTURE, AND BIOLOGICAL ACTIVITY OF NOVEL BISPIDINE DERIVATIVES

Objective: Derivatives of 3,7-diazabicyclo[3.3.1]nonan-9-one attract considerable attention from pharmacists for the treatment of a wide rangeof diseases. According to this interest, the novel derivatives of 3-cyclopropanmethyl-7-alkoxyalkyl-3,7-diazabicyclo[3.3.1]nonan-9-one withisopropoxypropyl and ethoxypropyl substituents in the position 7 had been synthesized to study their biological activity and toxicity. The practicalsignificance of the work is in the accumulation and development of scientific representations about diazabicyclic compounds, methods for theirsynthesis, structure, and properties, which can subsequently be used in a targeted design and identification of even more complex systems, as wellas in the development of further research in the field of 3,7-diazabicyclo[3.3.1]nonanes. For this purpose, complexes of the synthesized compoundswith β-cyclodextrin are obtained and their biological activity is investigated at the Department of Pharmacology of S.D. Asfendiyarov Kazakh NationalMedical University with the aid of the pharmacological tests.Methods: An experimental study of local anesthetic activity on the models of infiltration, conduction anesthesia, and acute toxicity of synthesizedmolecules was carried out using primary screening methods.Results: As a result of pharmacological screening, it has been found that the compounds exhibit local anesthetic activity and low toxicity and wasrecommended for in-depth study of their pharmacological properties.Conclusion: It turned out that a nature of the N-alkoxyalkyl radical does not affect the toxicity of cyclopropanmethyl- substituted bispidines. In theseries of O-benzoyloximes of bispidinones, the isopropoxypropyl- substituted analog is 1.3 times less toxic than ethoxypropyl- one.

Local Anesthetics: A Century of Progress

Summary One century after the clinical introduction of cocaine, local anesthesia remains the most important method of pain control in dentistry. Many local anesthetics have been marketed since 1884, and it is likely that attempts to produce drugs that enhance anesthetic efficacy, reduce systemic and local toxicity, and increase nociceptive selectivity, will continue. In addition, new methods of drug administration have been and will be developed to achieve these goals. Of fundamental importance to such improvements are investigations into the pharmacology of drugs with local anesthetic activity and anatomical and physiologic studies pertaining to the reasons why local anesthetics sometimes fail to achieve desired results. This paper reviews recent advances in our understanding of these drugs and their clinical use.