Accentuation of general anaesthetic activity of ketamine by glutamate NMDA (N-methyl D-aspartate) receptor antagonist

M. S. Umamageswari, Vasanthan ., Nikitha S. Kumar


Background: The aim of the present study was to evaluate the potentiation of general anaesthetic activity of ketamine by NMDA receptor antagonist ‘amantadine’ in wistar albino rats.

Methods: The wistar albino rats of either sex were divided into three groups of five animals in each group. Group I received ketamine 80mg/kg, group II received ketamine 40mg/kg along with amantadine 40mg/kg and group III received ketamine 80mg/kg along with amantadine 40mg/kg to evaluate the potentiation of general anaesthetic effect of ketamine. The sleep latency time and the total sleeping time were measured in all the three groups.

Results: The sleep latency time of group III is significantly decreased (p <0.035) and as equal to that of group II when compared to group I. The sleeping time of group III is significantly increased (p <0.001) when compared to group I.

Conclusions: Amantadine - the NMDA receptor antagonist potentiates the general anaesthetic activity of ketamine.


Amantadine, General anaesthetic effect, Ketamine, NMDA receptor antagonist

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McNamara JO. Pharmacotherapy of the Epilepsies. In: Brunton L, Chabner B, Knollman B. eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New Delhi:McGraw Hill Medical; 2011.

Tripathi, KD. Essentials of Medical Pharmacology. 7th ed. New Delhi: Jaypee Brothers Medial Publishers (P) Ltd; 2010.

Whoint. Available at: Accessed on September 2016.

Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson, G. Rang and Dale's Pharmacology. 7th ed. New York: Elsevier Churchill Livingstone;2012.

Iversen L, Dargan P. Ketamine: a review of use and harm. London: Advisory Council on the Misuse of Drugs. 10th December 2010. Available at:

Mion G, Villevieille T. Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS Neurosci Therapeutics. 2013 Jun;19(6):370-80.

Finkel R, Cubeddu LX, Clark MA. Lippincott’s Illustrated Reviews: Pharmacology. 4th ed. New Delhi:Lippincott’s Williams & Wilkins;2009.

Dietrich DE, Bode L, Spannhuth CW, Lau T, Huber TJ, Brodhun B, et al. Amantadine in depressive patients with Borna disease virus (BDV) infection: an open trial. Bipolar Disorders. 2000 Mar;2(1):65-70.

Ferszt R, Kühl KP, Bode L, Severus EW, Winzer B, Berghöfer A, et al. Amantadine revisited: an open trial of amantadinesulfate treatment in chronically depressed patients with Borna disease virus infection. Pharmacopsychiatry. 1999 Jul;32(04):142-7.

Hosenbocus S, Chahal R. Amantadine: a review of use in child and adolescent psychiatry. J Canadian Academy Child Adolescent Psychiatry. 2013 Feb;22(1):55.

Upstateedu. 1. Upstateedu. Available at: Accessed 3 September 2016.

Vogel GH, Vogel WH, Ascholkens B, Sandow J, Muller G, Wolfgang F, eds. Vogel Drug Discovery and Evaluation. 2nd ed. Berlin: Springer Verlag;2002:495-496.

Miyasaka M, Domino EF. Neuronal mechanisms of ketamine-induced anesthesia. Int J Neuropharmacol. 1968;7:557-73.

Abdelmawgoud A, Rashwan S. Effect of preoperative oral amantadine on intraoperative anesthetic and analgesic requirements in female patients during abdominoplasty. Egyptian J Anaesthesia. 2013 Jan 1;29(1):7-11.

Daniell LC. The noncompetitive N-methyl-D-aspartate antagonists, MK-801, phencyclidine and ketamine, increase the potency of general anesthetics. Pharmacol Biochem Behavior. 1990 May 1;36(1):111-5.

Budhiraja S, Singh J. Adjuvant effect of melatonin on anesthesia induced by thiopental sodium, ketamine, and ether in rats. Methods Findings Experimental Clin Pharmacol. 2005 Dec 1;27(10):697-700.

Imre G, Fokkema DS, Den Boer JA, Ter Horst GJ. Dose–response characteristics of ketamine effect on locomotion, cognitive function and central neuronal activity. Brain Res Bull. 2006 Apr 14;69(3):338-45.

Snijdelaar DG, Koren G, Katz J. Effects of perioperative oral amantadine on postoperative pain and morphine consumption in patients after radical prostatectomy results of a preliminary study. J Am Soc Anesthesiol. 2004 Jan 1;100(1):134-41.

Dehar NA, Walia RA, Ratol SU. Potentiation of thiopentone sodium induced hypnosis by Berberis aristata in rodents. Asian J Pharmaceut Clin Res. 2012;5(1):131-3.