General Anaesthetic / Hypnotic Activity of JV2015 in Mice and Rabbits

Total Page：16

File Type：pdf, Size：1020Kb

General Anaesthetic / Hypnotic Activity of JV2015 in Mice and Rabbits

Proceedings of the British Pharmacological Society at http://www.pA2online.org/abstracts/Vol13Issue3abst025P.pdf General Anaesthetic / Hypnotic Activity of JV2015 in Mice and Rabbits Currently, only few effective intravenous general anaesthetic agents are available for induction and maintenance of anaesthesia.These drugs have certain limitations in routine use. Flavonoids have been shown to possess central nervous system depressant effect mediated through the ionotropic GABA A receptors present in the CNS (1). Studies have demonstrated the sedative effect of a few flavonoid compounds (2). Compounds with hypnotic property can be used as intravenous general anaesthetic agents. The aim of the present study was to investigate a synthetic flavonecompound JV2015 for its general anaesthetic / hypnotic activity in mice and rabbits. Adult swiss albino mice (n=8) of both sex (20 – 30g) were injected with the test compound (30, 40 or 50 mg/kg) or thiopentone (25mg/kg) in a volume of 0.2ml through the tail vein over a period of 10sec (3). In Newzealand white rabbits (n=6) of both sex (1.5 – 2.0kg) the test compound (25 or 30mg/kg) was injected through marginal ear vein over a period of 30sec. The sleeping time was recorded and compared with the vehicle and standard control. The experimental protocol was approved by the Institutional Animal Ethics Committee. Data are expressed as mean ± S.E.M. Statistical analysis was performed using ANOVA followed by Post hoc Dunnett’s ‘t’ test (SPSS v.16) Thiopentone resulted in an immediate hypnotic effect in mice lasting for a period of 5.75 ± 0.27min. The test compound in doses of 30, 40 & 50mg/kg produced hypnosis that lasted for a period of 4.31 ± 0.17min , 4.50 ± 0.29min and 7.63 ±0.50 min respectively (Fig. 1). In rabbits, the duration of sleeping time was 9.00 ± 0.58min and 20.67 ± 0.72min with 25 and 30 mg/kg dose respectively (Fig. 2). The present study has clearly demonstrated the hypnotic effect of JV2015 and also identified a novel candidate drug with a potential to develop in to an ultra short acting intravenous general anaesthetic agent. 1. Fernandez SP et al., (2006). Eur J Pharmacol 539: 168–176. 2. Karim N et al., (2012). Br J Pharmacol 165: 880–896. 3. Glen JB. (1980). Br J Anaesth 52: 731–742. .

Copy Link

Recommended publications

Ketamine for Paediatric Sedation/Analgesia in the Emergency Department
275 Emerg Med J: first published as 10.1136/emj.2003.005769 on 22 April 2004. Downloaded from CLINICAL TOPIC REVIEW Emerg Med J: first published as 10.1136/emj.2003.005769 on 22 April 2004. Downloaded from Ketamine for paediatric sedation/analgesia in the emergency department M C Howes ............................................................................................................................... Emerg Med J 2004;21:275–280. doi: 10.1136/emj.2003.005769 This review investigates the use of ketamine for paediatric pain or other noxious stimuli, with relative preservation of respiratory and cardiovascular sedation and analgesia in the emergency department functions despite profound amnesia and analge- ........................................................................... sia,10 30–32 described as ‘‘cataleptic.’’10 This trance- like state of sensory isolation provides a unique combination of amnesia, sedation, and analge- he injured child presents a challenge to sia.7103031 The eyes often remain open, though emergency department (ED) practitioners. nystagmus is commonly seen. Heart rate and The pain and distress can be upsetting for T blood pressure remain stable, and are often staff as well as parents. The child’s distress can stimulated, possibly through sympathomimetic be compounded by the fear of a painful actions.30 31 33 Functional residual capacity and procedure to follow, previous conditioning from tidal volume are preserved, with bronchial unexpected ‘‘jabs’’ when receiving immunisa- smooth muscle relaxation34–37 and maintenance tions, or previous visits to an ED.1 of airway patency and respiration.10 30 31 38 As doctors we strive to relieve pain and However, despite the enthusiasm of many suffering, and swear to do no harm. Forced authors and practitioners, ketamine may not be restraint, still performed in some departments in the ideal agent.
[Show full text]
A Comparative Study of Anaesthetic Agents on High Voltage Activated Calcium
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.17.423182; this version posted December 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. A COMPARATIVE STUDY OF ANAESTHETIC AGENTS ON HIGH VOLTAGE ACTIVATED CALCIUM CHANNEL CURRENTS IN IDENTIFIED MOLLUSCAN NEURONS Terrence J. Morris1, Philip M. Hopkins2,3 and William Winlow4,5 1Department Science and Technology - Biology, Douglas College, 700 Ryal Avenue, New Westminster, British Columbia, Canada; 2 Leeds Institute of Medical Research at St James’s, School of Medicine, University of Leeds, Leeds, United Kingdom; 3Malignant Hyperthermia Investigation Unit, Leeds Institute of Molecular Medicine, St. James’s University Hospital, Leeds, LS9 7TF, United Kingdom; 4 Department of Biology, University of Naples Federico II, Via Cintia 26, 80126, Naples, Italy; 5Institute of Ageing and Chronic Diseases, University of Liverpool, Liverpool, United Kingdom. Corresponding author: William Winlow Key Words: General anaesthetic, calcium channels, Lymnaea, light yellow cells SUMMARY 1. Using the two electrode voltage clamp configuration, a high voltage activated whole-cell Ca2+ channel current (IBa) was recorded from a cluster of neurosecretory ‘Light Yellow’ Cells (LYC) in the right parietal ganglion of the pond snail Lymnaea stagnalis. 2. Recordings of IBa from LYCs show a reversible concentration-dependent depression of current amplitude in the presence of the volatile anaesthetics halothane, isoflurane and sevoflurane, or the non-volatile anaesthetic pentobarbitone at clinical concentrations. 3. In the presence of the anaesthetics investigated, IBa measured at the end of the depolarizing test pulse showed proportionally greater depression than that at measured peak amplitude, as well as significant decrease in the rate of activation or increase in inactivation or both.
[Show full text]
Dionaea Muscipula)
bioRxiv preprint doi: https://doi.org/10.1101/645150; this version posted May 22, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 RESEARCH PAPER 2 Anaesthesia with diethyl ether impairs jasmonate signalling in the 3 carnivorous plant Venus flytrap (Dionaea muscipula). 4 Andrej Pavlovič1*, Michaela Libiaková2, Boris Bokor2,3, Jana Jakšová1, Ivan Petřík4, Ondřej 5 Novák4, František Baluška5 6 1 Department of Biophysics, Centre of the Region Haná for Biotechnological and Agricultural 7 Research, Faculty of Science, Palacký University, Šlechtitelů 27, CZ-783 71, Olomouc, Czech 8 Republic 9 2 Department of Plant Physiology, Faculty of Natural Sciences, Comenius University in 10 Bratislava, Ilkovičova 6, Mlynská dolina B2, SK-842 15, Bratislava, Slovakia 11 3 Comenius University Science Park, Comenius University in Bratislava, Ilkovičova 8, SK-841 12 04, Bratislava, Slovakia 13 4 Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and 14 Agricultural Research, Institute of Experimental Botany CAS and Faculty of Science, Palacký 15 University, Šlechtitelů 27, CZ-783 71, Olomouc, Czech Republic 16 5IZMB, University of Bonn, Kirschallee 1, 53115 Bonn, Germany 17 *- author for correspondence: [email protected], +420 585 634 831 18 Running title: Anaesthetic impairs jasmonate signalling in carnivorous plant 19 Highlight: Carnivorous plant Venus flytrap (Dionaea muscipula) is unresponsive to insect 20 prey or herbivore attack due to impaired electrical and jasmonate signalling under general 21 anaesthesia induced by diethyl ether.
[Show full text]
Nerve Blocks for Surgery on the Shoulder, Arm Or Hand
The Association of Regional The Royal College of Anaesthetists of Great Anaesthesia – Anaesthetists Britain and Ireland United Kingdom Nerve blocks for surgery on the shoulder, arm or hand Information for patients and families www.rcoa.ac.uk/patientinfo First edition 2015 This leaflet is for anyone who is thinking about having a nerve block for an operation on the shoulder, arm or hand. It will be of particular interest to people who would prefer not to have a general anaesthetic. The leaflet has been written with the help of patients who have had a nerve block for their operation. You can find more information leaflets on the website www.rcoa.ac.uk/patientinfo. The leaflets may also be available from the anaesthetic department or pre-assessment clinic in your hospital. The website includes the following: ■ Anaesthesia explained (a more detailed booklet). ■ You and your anaesthetic (a shorter summary). ■ Your spinal anaesthetic. ■ Anaesthetic choices for hip or knee replacement. ■ Epidural pain relief after surgery. ■ Local anaesthesia for your eye operation. ■ Your child’s general anaesthetic. ■ Your anaesthetic for major surgery with planned high dependency care afterwards. ■ Your anaesthetic for a broken hip. Risks associated with your anaesthetic This is a collection of 14 articles about specific risks associated with having an anaesthetic or an anaesthetic procedure. It supplements the patient information leaflets listed above and is available on the website: www.rcoa.ac.uk/patients-and-relatives/risks. Throughout this leaflet and others in the series, we have used this symbol to highlight key facts. 2 NERVE BLOCKS FOR SURGERY ON THE SHOULDER, ARM OR HAND Brachial plexus block? The brachial plexus is the group of nerves that lies between your neck and your armpit.
[Show full text]
Local Anaesthetic Informed Consent
Local anaesthetic Informed consent: patient information This information sheet answers frequently asked questions about having local anaesthetic. It has been developed to be used in discussion with your doctor or healthcare professional. 1. What is local anaesthetic and how will 3. What are my specific risks? it help me? There may also be risks specific to your A local anaesthetic is used to numb a small individual condition and circumstances. Your part of your body and stop you feeling pain. doctor/healthcare professional will discuss You will be awake and aware of what is these with you. Ensure they are written on the © The State of Queensland (Queensland Health) 2017 Health) (Queensland Queensland of State The © To request permission email: [email protected] email: permission request To happening. Local anaesthetic is used when consent form before you sign it. nerves can be easily reached by drops, sprays, 4. What are the risks of not having this ointments or injections. anaesthetic? Except as permitted under the Copyright Act 1968, no part of this work may be may work this no part of 1968, Act the Copyright under permitted as Except Local anaesthetic generally has less side-effects reproduced communicated or adapted without permission from Queensland Health Queensland from permission without or adapted communicated reproduced and risks than a general anaesthetic (which is There may be consequences if you choose not to also generally a safe procedure if required). have the proposed anaesthetic. Please discuss these with your doctor/healthcare professional. For some procedures or operations, sedation is given with local anaesthetic.
[Show full text]
Anaesthesia for Cancer Patients Mujeebullah Rauf Arain and Donal J
Anaesthesia for cancer patients Mujeebullah Rauf Arain and Donal J. Buggy Purpose of review Introduction Cancer is beginning to outpace cardiovascular disease as Cancer is the second leading cause of death in the devel- the primary cause of death in the developed world. A oped world, accounting in 2004 for over half a million majority of cancer patients will require anaesthesia either for deaths. Cancers at four organ sites – lung/bronchus, colo- primary debulking tumour removal or to treat an adverse rectal, breast and prostate – accounted for 56% of all consequence of the malignant process or its treatment. cancer cases and 53% of all cancer deaths [1]. Approxim- Therefore we outline here the pathophysiology of cancer, ately half of patients diagnosed with cancer will develop generalized metastatic disease and systemic chemotherapy metastatic disease. Over 70% of all cancer patients develop and radiotherapy on major organ systems. The anaesthetic symptoms from either their primary or metastatic disease considerations for optimum perioperative management of [2]. The overall metastatic burden and the number and cancer patients are discussed, and the possibility of location of the sites involved by disease inﬂuence prog- anaesthetic technique at primary cancer surgery affecting nosis. There is an increasing surgical intervention rate long-term cancer outcome is mentioned. in cancer patients, both for primary tumour excision Recent ﬁndings and emergency intervention for intercurrent illness. Cancer and its therapy can adversely affect every major Coupled with the increased use of chemotherapeutic organ system with profound implications for perioperative agents over the past decade, cancer patients requiring management. Retrospective analysis suggests an surgery present particular challenges for the anaesthe- association between regional anaesthetic techniques at tist [2].
[Show full text]
An Introduction to Anaesthesia
What You Need to KNoW about An introduction to anaesthesia Introduction divided into three stages: induction, main- n Central neuraxial block, e.g. spinal or Anaesthetic experience in the undergradu- tenance and emergence. epidural (Figure 1 and Table 1). ate timetable is often very limited so it can In regional anaesthesia, nerve transmis- remain somewhat of a mysterious practice sion is blocked, and the patient may stay Components of a general well into specialist training. This introduc- awake or be sedated or anaesthetized dur- anaesthetic tion to the components of an anaesthetic ing a procedure. Techniques used include: A general anaesthetic always involves an will help readers to get more from clinical n Local anaesthetic field block hypnotic agent, usually an analgesic and attachments in surgery and anaesthetics or n Peripheral nerve block may also include muscle relaxation. The serve as an introduction to the topic for n Nerve plexus block combination is referred to as the ‘triad of novice or non-anaesthetists. anaesthesia’. Figure 1. Schematic vertical longitudinal section The relative importance of each com- Types and sites of anaesthesia of vertebral column and structures encountered ponent depends on surgical and patient The term anaesthesia comes from the when performing central neuraxial blocks. * factors: the intervention planned, site, Greek meaning loss of sensation. negative pressure space filled with fat and surgical access requirement and the Anaesthetic practice has evolved from a venous plexi. † extends to S2, containing degree of pain or stimulation anticipated. need for pain relief and altered conscious- arachnoid mater, CSF, pia mater, spinal cord The technique is tailored to the individu- ness to allow surgery.
[Show full text]
General Anaesthetic Informed Consent
General anaesthetic Informed consent: patient information This information sheet answers frequently asked questions about having a general anaesthetic. It has been developed to be used in discussion with your doctor or healthcare professional. 1. What is a general anaesthetic? 4. What are the risks of having an Source of images: Shutterstock images: of Source A general anaesthetic (sometimes referred to as anaesthetic? a “GA”) is a mixture of medicines to keep you Modern anaesthesia is generally very safe. unconscious and pain free during an operation Every anaesthetic has a risk of side effects or procedure. Medicines are injected into a vein and complications. Whilst these are usually © The State of Queensland (Queensland Health) 2017 Health) (Queensland Queensland of State The © To request permission email: [email protected] email: permission request To and/or breathed in as gases into the lungs. To temporary, some may cause long-term give the gases, the anaesthetist will use a face problems. mask and/or a breathing tube which will be Common side effects and complications placed through your mouth or nose and into Except as permitted under the Copyright Act 1968, no part of this work may be may work this no part of 1968, Act the Copyright under permitted as Except include: reproduced communicated or adapted without permission from Queensland Health Queensland from permission without or adapted communicated reproduced your throat. The tube is removed as you wake up • nausea and/or vomiting after surgery. • headache • pain and/or bruising at injection sites • sore or dry throat and lips • minor damage to lips • blurred/double vision • dizziness and feeling faint • mild allergic reaction such as itching or a rash • problems passing urine • shivering • damage to teeth and dental work Image 1: Patient with general anaesthetic being given with a face mask • confusion and memory loss, usually in older 2.
[Show full text]
Dexmedetomidine Accord ,INN-Dexmedetomidine
ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT Dexmedetomidine Accord 100 micrograms/ml concentrate for solution for infusion 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each 1 ml of concentrate contains dexmedetomidine hydrochloride equivalent to 100.0 micrograms dexmedetomidine. Each 2 ml vial contains 200 micrograms of dexmedetomidine. Each 4 ml vial contains 400 micrograms of dexmedetomidine. Each 10 ml vial contains 1000 micrograms of dexmedetomidine. The concentration of the final solution after dilution should be either 4 micrograms/ml or 8 micrograms/ml. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Concentrate for solution for infusion (sterile concentrate). The concentrate is a clear, colourless solution, pH 4.5 – 7.0 4. CLINICAL PARTICULARS 4.1 Therapeutic indications For sedation of adult ICU (Intensive Care Unit) patients requiring a sedation level not deeper than arousal in response to verbal stimulation (corresponding to Richmond Agitation-Sedation Scale (RASS) 0 to -3). For sedation of non-intubated adult patients prior to and/or during diagnostic or surgical procedures requiring sedation, i.e. procedural/awake sedation. 4.2 Posology and method of administration For sedation of adult ICU (Intensive Care Unit) patients requiring a sedation level not deeper than arousal in response to verbal stimulation (corresponding to Richmond Agitation-Sedation Scale (RASS) 0 to -3). For hospital use only. Dexmedetomidine Accord should be administered by healthcare professionals skilled in the management of patients requiring intensive care. Posology Patients already intubated and sedated may switch to dexmedetomidine with an initial infusion rate of 0.7 micrograms/kg/h which may then be adjusted stepwise within the dose range 0.2 to 1.4 micrograms/kg/h in order to achieve the desired level of sedation, depending on the patient’s response.
[Show full text]
Interaction of Cannabis and General Anaesthetic Agents in Mice G.B
Br. J. Pharmac. (1974), 50, 593-599 INTERACTION OF CANNABIS AND GENERAL ANAESTHETIC AGENTS IN MICE G.B. CHESHER, D.M. JACKSON & G.A. STARMER Department of Pharmacology, University of Sydney, Sydney 2006, Australia 1 A cannabis extract (I) (in a concentration equivalent to 10 mg A9-tetrahydro- cannabinol(THC)/kg) prolonged pentobarbitone anaesthesia in mice maximally 20 min to 2 h after medication. The effect was still significant after 8 h, but less than at 2 hours. 2 The cannabis extract (1) (equivalent to 10 mg A9-THC/kg) prolonged both pentobarbitone and ether anaesthesia in mice when administered 20 min before the anaesthetic. After eight consecutive daily doses of cannabis, the pentobarbitone anaesthesia was still significantly longer than a control group, while ether anaesthesia was not significantly prolonged. 3 A second cannabis extract (II) with a different ratio of cannabinoids (also administered in dosage equivalent to 10 mg A9-THC/kg) failed to affect pentobarbitone anaesthesia in mice. This extract presented about 4% the dose of cannabidiol as extract I. 4 A8-THC, A9-THC and cannabidiol prolonged pentobarbitone anaesthesia with cannabidiol being generally more active than A 9 -THC. Cannabinol ( 10 mg/kg) was inactive. 5 The effects of cannabidiol and A9-THC were found to be additive, and there was a consistent trend for cannabinol to reduce the effectiveness of A9-THC and cannabidiol when given in combination. 6 Premedication with phenoxybenzamine, phentolamine, propranolol, iproniazid, protripty- line, desipramine, reserpine, ai-methyl tyrosine or parachlorophenylalanine did not affect the extract I-induced prolongation of pentobarbitone anaesthesia. 7 It is concluded that cannabis may affect pentobarbitone and ether anaesthesia in mice at least partially by a direct depressant effect, and that the cannabis-induced prolongation of anaesthesia is probably unrelated to any effect on central 5-hydroxytryptamine or catechol- amine neurones.
[Show full text]
Local Anaesthesia for Your Eye Operation
The Association of The Royal College of Anaesthetists of Anaesthetists Great Britain and Ireland Local anaesthesia for your eye operation Information for patients www.rcoa.ac.uk/patientinfo Fourth edition 2014 This leaflet explains what to expect when you have an eye operation with a local anaesthetic. It has been written by patients, patient representatives and anaesthetists, working together. You can find more information in other leaflets in the series on the website www.rcoa.ac.uk/patientinfo. The leaflets may also be available from the anaesthetic department or pre-assessment clinic in your hospital. The website includes the following: ■ Anaesthesia explained (a more detailed booklet) ■ You and your anaesthetic (a shorter summary) ■ Your spinal anaesthetic ■ Anaesthetic choices for hip or knee replacement ■ Epidural pain relief after surgery ■ Your child’s general anaesthetic ■ Your anaesthetic for major surgery ■ Your anaesthetic for a broken hip ■ Brachial plexus block for surgery and pain relief Risks associated with your anaesthetic This is a collection of 14 articles about specific risks associated with having an anaesthetic or an anaesthetic procedure. It supplements the patient information leaflets listed above and is available on the website: www.rcoa.ac.uk/patients-and-relatives/risks. Throughout this leaflet and others in the series, we have used this symbol to highlight key facts. 2 LOCAL ANAESTHESIA FOR YOUR EYE OPERATION Local anaesthetic for an eye operation A local anaesthetic is a drug that stops you feeling pain. For eye surgery, it can be given as eye drops and/or injections. After you have the local anaesthetic you will still be awake and aware of what is happening to you.
[Show full text]
A Guide to the Administration of Medicines in the Perioperative
......„„.....NHS Grampian Guideline For The Administration Of Medicines In The Pen-Operative Period Co-ordinators: Consultation Group: Approver: Pre-Operative Assessment See Consultation list Medicine Guidelines and Pharmacist Policies Group Signature: Signature: ...i 0 0 a Identifier: Review Date: Date Approved: NHSG/Guid/Peri0p/ May 2022 May 2019 MGPG1026 Uncontrolled when printed Version 3 Executive Sign-Off This document has been endorsed by the Director of Pharmacy and Medicines Management Signature: Title: Guideline for the Administration of Medicines in the Peri- Operative Period Unique Identifier: NHSG/Guid/PeriOp/MGPG1026 Replaces: NHSG/Guid/PeriOp/MGPG697, Version 2 Across NHS Organisation Directorate Clinical Service Sub Boards Wide Department Area This controlled document shall not be copied in part or whole without the express permission of the author or the author’s representative. Lead Author/Co-ordinator: Pre-Operative Assessment Pharmacist Subject (as per document Clinical Guidance registration categories): Key word(s): Peri-operative medication guidance, gastro intestinal system, cardiovascular system, respiratory, central nervous, infections, endocrine, obstetrics, gynaecology, urinary tract, malignant, nutrition, blood, musculoskeletal, joint, corticosteroid treatment, alternative routes, antiepileptic Process Document: Policy, Guideline Protocol, Procedure or Guideline Document application: NHS Grampian Purpose/description: This policy is designed to be used by pharmacy, nursing and medical staff at pre-assessment
[Show full text]