DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20182070

Effect of promethazine on seizure activity and its interactions with antiepileptic drugs diazepam and phenytoin in Rats

Sandesh Warudkar, Vinod Shinde, Archana Borkar

Abstract


Background: Current antiepileptic drugs (AEDs) are effective in controlling seizures in about 70% patients but use is often limited by adverse effects. Promethazine, H1 receptor antagonist, has a controversial status in patients of epilepsy. Both pro and antiepileptic effect has been documented in various animal studies. Hence, this study was designed to see the effect of promethazine, an H1 antihistaminic drug and its interactions with antiepileptic drugs in rats.

Methods: The effect of promethazine (10mg/kg) and its interactions with antiepileptic drugs diazepam and phenytoin was assessed by using maximal electroshock seizures (MES) and chemoshock (PTZ) method.

Results: Promethazine along with diazepam in subtherapeutic doses exerted significant protection against MES induced seizures whereas no such protection was observed with PTZ method rather the seizure threshold was reduced.

Conclusions: Subtherapeutic doses of Promethazine alone and in combination with diazepam showed protection against seizures in MES method. However, proconvulsant effect was seen with PTZ method suggesting histamine plays a protective role in development of seizures. This shows dual behavior of promethazine on MES and PTZ induced seizures.


Keywords


Diazepam, MES, Pentylenetetrazol, Phenytoin, Promethazine

Full Text:

PDF

References


Disease GBD, Injury I, Prevalence C. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the global burden of disease study 2015. Lancet. 2016;388(10053):1545-602.

World Health Organization. Epilepsy. Fact sheet No. 999. January 2009. Available at: http://www.who.int/mediacentre/ factsheets/fs999/en/print.html. Accessed 7/23/2013

Brodie MJ, Elder AT, Kwan P. Epilepsy in later life. The Lancet Neurology. 2009;8(11):1019-30.

Holmes, Thomas R. Browne, Gregory L. Handbook of epilepsy (4th Ed.). Philadelphia: Lippincott Williams and Wilkins; 2008:7. ISBN 978-0-7817-7397-3. Archived from the original on 29 May 2016.

Wyllie's treatment of epilepsy: principles and practice (5th Ed.). Philadelphia: Wolters Kluwer/Lippincott Williams and Wilkins; 2010. ISBN 978-1-58255-937-7. Archived from the original on 24 June 2016.

Newton CR. Epilepsy in poor regions of the world. The Lancet. 2012;380(9848):1193-201.

Rang HP, Dale MM. Antiepileptic drugs, In: Pharmacology 5th Edition; Churchil Livingstone, Elsevier sciences Limited, Edinburgh; 2003:550.

Schlienger RG, Shear HN. Antiepileptic drug hypersensitivity syndrome. Epilepsia. 1998;39(7):S3-7.

Hennino A, Berard F, Guillot I, Saad N, Rozières A, Nicolas JF. Pathophysiology of urticaria. Clin Rev Allergy Immunol. 2006;30:3-11.

Drain KL, Volcheck GW. Preventing and managing drug induced anaphylaxis. Drug Saf. 2001;24:843-53.

Tedeschi DH, Benigni JP, Elder CJ. Effects of various phenothiazines on minimal electroshock seizure threshold and spontaneous motor activity of mice. The J of Phar and Exp Therapeu (JPET). 1958;123:35-8.

Kamel C, Ohuch M, Sugimoto Y, Okuma C. Mechanism responsible for epileptogenic activity by first generation H1 antagonists in rats. Brain Res. 2000;887(1):183-6.

Scherki R, Hashem A, Frey H. Histamine in brain, its role in regulation of seizure susceptibility. Epilepsy Research. 1991;10:111-18.

Saper CB, Chou TC, Scammell TE. The sleep switch: Hypothalamic control of sleep and wakefulness. Trends Neurosci. 2001;24:726-31.

Sen P, Khanna N, Ray A. Histaminergic mechanisms in experimental convulsions. Indian J Exp Biol. 1991 Apr;29(4):375-8.

Saxena VC, Bapat SK, Dhawan BN. An experimental evaluation of the anticonvulsant activity of some antihistaminic drugs. Jap J Pharmacol. 1969;19:477-84.

Tanaka K, Kawasaki Y. A group of compounds possessing anticonvulsant activity in the maximal electroshock seizure in rats. Jap J Pharmacol 1957;6:115-21.

Dashputra AV, Borkar AS, Hemnani TJ, Badwaik RT. Effect of ketamine on seizure activity and its interactions with antiepileptic drugs in rats. IJMPS. 2012;03(02):01-8.

Huwiler A. Electroshock in mice. In: Vogel HG, editor. Drug Discovery and Evaluation: Pharmacological Assays. 3rd Ed, Vol. 1. Springer-Verlag: Berlin, New York; 2008:692-693.

Swinyard EA, Brown WC, Goodman. Comparitive assay of antiepileptic drugs in mice and rats. J pharmacol express Ther. 1952;106:319.

Huwiler A. Pentylenetetrazole (Metrazol) induced convulsions. In: Vogel HG, editor. Drug Discovery and Evaluation: Pharmacological Assays. 3rd Ed, Vol. 1. Springer-Verlag: Berlin, New York; 2008:613-614.

Richard RK, Everett GM. Analgesics and anticonvulsant properties of 3,5,5 trimethylloxazolidine, 2-4 dione (Tridione). Fed Proc. 1944:39-44.

Saras A, Glosslmann G, Vogt- Elsele AK, Erlkamp KS. Histamine action on vertebrate GABAA receptors. Direct channel gating and potentiation of GABA responses., The J of Bio Chemis. 2008;283(16):10410-475.

Sangalli BC. Role of histaminergic neuronal system in the CNS toxicity of the first generation H1 antagonists. Progress in Neurobiology. 1997;52(2):145-57.

Hovart A, Momic T, Bunjac A, Petrovic S. Selective Inhibition of brain Na,K- ATPase by drugs. Physiol. 2006;55:325-38.

Kai MS, Hirvonen MR. Second messengers in cholinergic induced convulsions and neuronal injury. Toxicology Letters. 1992;437-45.

Belousov AB, O’hara BF, Denisova JV. Acetylcholine becomes the major excitatory neurotransmitter in the hypothalamus in vitro in the absence of glutamate excitation, The J of Neurosc. 2001;21(6):2015-17.

Stahl SM. Stahl’s Essentials Psychopharmacology, 3rd Edition, NewYork, NY Cambridge Univerity Press; 2008:1027-1034.

Hass H, Paulima P. Histaminergic system in brain, Nat Rev Neurosci. 2003;121-30.