Advertisement
Research Article| Volume 19, ISSUE 6, P403-407, September 1997

Download started.

Ok

Therapeutic doses of theophylline exert proconvulsant effects in developing mice

DOI:https://doi.org/10.1016/S0387-7604(97)00051-X
Therapeutic doses of theophylline exert proconvulsant effects in developing mice
Previous ArticleLamotrigine as add-on drug in children and adolescents with refractory epilepsy and mental delay: an open trial
Next ArticleChildhood occipital epilepsy: seizure manifestations and electroencephalographic features
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      We studied the effect of therapeutic doses of theophylline on electrically-induced convulsions in developing mice. A theophylline dose as small as 3 mg/kg increased seizure susceptibility of 21-day-old mice, but not of 42-day-old mice. These findings were consistent with clinical reports that theophylline at the therapeutic blood concentrations occasionally induced convulsions in children. The age-dependent proconvulsant effect of theophylline was well inhibited by phenobarbital (PB), dose-dependently, but not by other well-established antiepileptic drugs (AEDs). PB may be a good choice of AED in patients with bronchial asthma and seizure disorders, if PB is indicative for their seizure types. The proconvulsant effect of theophylline in 21-day-old mice was counteracted by not only an adenosine A1 agonist, but also an NMDA antagonist and a histamine H3 antagonist. Several studies have established that the proconvulsant effect of theophylline intoxication is mainly due to the blockade of adenosine A1 receptors. The present findings suggested that the proconvulsant properties of therapeutic doses of theophylline in developing period were different from those of theophylline intoxication. Combination of therapeutic doses of theophylline and centrally-acting histamine H1 antagonists showed proconvulsant effects even in 42-day-old mice, suggesting that peripherally acting histamine H1 antagonists, such astemizole, evastine and epinastine, were much safer than centrally acting histamine H1 antagonists for patients with both allergy and seizure history.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Register: Create an account
      Institutional Access: Sign in to ScienceDirect

      Reference

        • Gaudreault P.
        • Guay J.
        Theophylline poisoning: pharmacological considerations and clinical management.
        Med. Toxicol. 1986; 1: 169-191
        • Pollock J.
        • Kiechel F.
        • Cooper D.
        • Weinberger M.
        Relationship of serum theophylline concentration to inhibition of exercise-induced brochopasm and comparison with cormolyn.
        Pediatrics. 1978; 60: 840-844
        • Zaccara G.
        • Muscas G.C.
        • Messori A.
        Clinical features, pathogenesis and management of drug-induced seizures.
        Drug Saf. 1990; 5: 109-151
        • Katsunuma T.
        • Tsubaki T.
        • Sakaguchi N.
        • Kawahara H.
        • Matsubara K.
        • Iikura Y.
        Theophylline in cerebrospinal fluid (in Japanese).
        Shouni-Rinsho-Yakuri-Kenkyukai-Zasshi. 1995; 2: 16-19
        • Dragunow M.
        Adenosine receptor antagonism accounts for the seizure-prolonging effects of aminophylline.
        Pharmacol. Biochem. Behav. 1990; 36: 751-755
        • Dragunow M.
        • Goddard G.V.
        • Laverty R.
        Proconvulsant effects of theophylline on hippocampal afterdischarges.
        Exp. Neurol. 1987; 96: 732-735
        • Sanders R.C.
        • Murray T.F.
        Temporal relationship between A1 adenosine receptor upregulation and alterations in bicuculline seizure susceptibility in rats.
        Neurosci. Lett. 1989; 101: 325-330
        • Yasuhara M.
        • Levy G.
        Effect of age on neurotoxicity of theophylline.
        J. Pharm. Sci. 1988; 77: 645-646
        • Yokoyama H.
        • Onodera K.
        • Iinuma K.
        • Watanabe T.
        Proconvulsive effects of histamine H1-antagonists on electrically-induced seizure in developing mice.
        Psychopharmacology. 1993; 112: 199-203
        • Caboche J.
        • Mitrovic N.
        • Le Saux F.
        • Besson M.J.
        • Sauter A.
        • Maurin Y.
        Postnatal evolution of the channel complex in the rat hippocampus.
        Exp. Neurol. 1990; 110: 237-247
        • McDonald J.W.
        • Johnson M.V.
        • Young A.B.
        Differential ontogenic development of three receptors comprising the NMDA receptor/channel complex in the rat hippocampus.
        Exp. Neurol. 1990; 110: 237-247
        • Insel T.R.
        • Miller L.P.
        • Gelhard R.E.
        The ontogeny of excitatory amino acid receptors in the rat forebrain — I.N-methyl-d-aspartate and quisqualate receptors.
        Neuroscience. 1990; 35: 31-43
        • Auritt W.A.
        • McGeady S.J.
        • Mansmann Jr., H.C.
        The relationship of cerebrospinal fluid and plasma theophylline concentrations in children adolescents taking theophylline.
        J. Allergy Clin. Immunol. 1985; 75: 731-735
        • Ramzan I.M.
        • Levy G.
        Kinetics of drug action in disease states. XVI. Pharmacodynamics of theophylline-induced seizures in rats.
        J. Pharmacol. Exp. Ther. 1986; 236: 708-713
        • Masuda Y.
        • Shiraishi Y.
        • Karasawa T.
        • Yoshida K.
        • Shimizu M.
        Differential antagonisms of anticonvulsants to the various components of maximal seizure induced by electroshock or pentylenetetrazole in mice.
        J. Pharm. Dyn. 1981; 3: 526-531
        • Czuczwar S.J.
        • Jackel R.
        • Loscher W.
        Effects of aminophylline and enprofylline on the protective activity of phenobarbital against amygdala-kindled seizures in rats.
        Epilepsy Res. 1987; 1: 234-238
        • Holmes G.L.
        • Thompson J.L.
        Effects of kainic acid on seizure susceptibility in the developing brain.
        Brain Res. 1988; 39: 51-59
        • Klishin A.
        • Lozavaya N.
        • Krishtal O.
        Persistently enhanced ratio of NMDA and non-NMDA components or rat hippocampal EPSC after block of A1 adenosine receptors at increased Ca2+o/Mg2+o.
        Neurosci. Lett. 1994; 179: 132-136
        • Velisek L.
        • Veliskova J.
        • Ptachewich Y.
        • Ortiz J.
        • Shinnar S.
        • Moshe S.L.
        Age-dependent effect of γ-aminobutyric acid agents on flurothil seizures.
        Epilepsia. 1995; 36: 636-643
        • Yokoyama H.
        • Onodera K.
        • Iinuma K.
        • Watanabe T.
        Effect of thioperamide, a histamine H3 receptor antagonist, on electrically induced convulsions in mice.
        Eur. J. Pharmacol. 1993; 234: 129-134
        • Yokoyama H.
        • Onodera K.
        • Maeyama K.
        • Sakurai E.
        • Iinuma K.
        • Leurs R.
        • et al.
        Clobenpropit (VUF-9153), a new histamine H3 receptor antagonist, inhibits electrically induced convulsions in mice.
        Eur. J. Pharmacol. 1994; 260: 23-28
        • Yoshimura K.
        • Hosokawa T.
        • Hashizume M.
        • Hamada F.
        • Morita H.
        • Kurashige T.
        3 cases of status epilepticus induced by theophylline (in Japanese).
        Shounika-Rinsho. 1993; 46: 317-321

      Article info

      Publication history

      Accepted: June 19, 1997
      Received in revised form: June 19, 1997
      Received: February 24, 1997

      Identification

      DOI: https://doi.org/10.1016/S0387-7604(97)00051-X

      Copyright

      © 1997 Elsevier Science B.V. All rights reserved. Published by Elsevier Inc.

      ScienceDirect

      Access this article on ScienceDirect

      The content on this site is intended for healthcare professionals.


      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the Cookie Preference Center for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties.


      RELX