Purinergic modulation of the seizure threshold for pentylenetetrazol in the rat

Thomas F. Murray, D. Sylvester, C. S. Schultz, P. Szot

Research output: Contribution to journalArticle

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Abstract

The effects of various metabolically-stable analogs of adenosine on the threshold for seizures in rats was determined by measuring the dose of pentylenetetrazol (PTZ), infused through a tail vein, required to elicit a myoclonic jerk. The adenosine receptor agonists, 2-chloroadenosine (2-ClAdo), cyclohexyladenosine (CHA) and l- and d-phenylisopropyladenosine (l- and d-Pia), all produced dose-dependent elevations of the seizure threshold for pentylenetetrazol in rats. l-Phenylisopropyl-adenosine was the most potent analog of adenosine tested with a dose as small as 5 μg/kg (i.v.) producing a 23% increase in seizure threshold for pentylenetetrazol. The rank order of the potency of adenosine agonists in increasing the seizure threshold was l-PIA > 2-ClAdo > CHA > d-PIA, with l-PIA being 79 times more potent than d-PIA. In contrast to these effects, the adenosine receptor antagonist, theophylline, elicited a proconvulsant effect in doses from 15 to 60 mg/kg (i.p.). The effect of theophylline in reducing seizure threshold for pentylenetetrazol peaked at 30 mg/kg, a dose which reduced the seizure threshold by approx. 27%. Support for the involvement of recognition sites for adenosine in the observed modulation of seizure threshold was provided by the antagonism of the elevation of the seizure threshold for pentylenetetrazol induced by 2-ClAdo, by pretreatment with theophylline (5 mg/kg, i.v.). These findings provide support for the idea that endogenous adenosine may function as a regulator of seizure susceptibility.

Original languageEnglish
Pages (from-to)761-766
Number of pages6
JournalNeuropharmacology
Volume24
Issue number8
DOIs
StatePublished - 1985
Externally publishedYes

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Pentylenetetrazole
Seizures
Adenosine
2-Chloroadenosine
Theophylline
Phenylisopropyladenosine
Purinergic P1 Receptor Agonists
Purinergic P1 Receptor Antagonists
Myoclonus
Tail
Veins

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Purinergic modulation of the seizure threshold for pentylenetetrazol in the rat. / Murray, Thomas F.; Sylvester, D.; Schultz, C. S.; Szot, P.

In: Neuropharmacology, Vol. 24, No. 8, 1985, p. 761-766.

Research output: Contribution to journalArticle

Murray, Thomas F. ; Sylvester, D. ; Schultz, C. S. ; Szot, P. / Purinergic modulation of the seizure threshold for pentylenetetrazol in the rat. In: Neuropharmacology. 1985 ; Vol. 24, No. 8. pp. 761-766.
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