ABSTRACT
It has been suggested that endogenous chemical substances, such as adenosine, released during a seizure attack, may act as anticonvulsants in vivo. We have investigated electrophysiologically the effects of purinoceptor agonists and antagonists on the epileptiform activity induced by intracortical digitalis in anesthetized rats. Intracortical injections of 1, 2, or 4 micrograms digitalis (desacetyl lanatocid C) caused an epileptiform electrocorticogram (ECoG). The application of adenosine (25 or 100 microM) or adenosine triphosphate (ATP) (3 mM) after desacetyl lanatocid C blocked the epileptiform activity. beta, gamma-Methylene ATP (0.1-0.8 mM), a stable analog of ATP, produced inhibition and then death. The epileptogenic effect of desacetyl lanatocid C was enhanced by theophylline (1 mM); however, suramin (1 mM) changed the pattern of epilepsy. These results indicate that the purinergic system may be involved in the mechanism of action of digitalis glycosides.
Subject(s)
Epilepsy/prevention & control , Lanatosides/antagonists & inhibitors , Purinergic Agonists , Purinergic Antagonists , Adenosine/pharmacology , Adenosine Triphosphate/analogs & derivatives , Adenosine Triphosphate/pharmacology , Animals , Electroencephalography/drug effects , Epilepsy/chemically induced , Female , Male , Phosphodiesterase Inhibitors/pharmacology , Rats , Rats, Wistar , Somatosensory Cortex/drug effects , Somatosensory Cortex/physiology , Suramin/pharmacology , Theophylline/pharmacologySubject(s)
Arrhythmias, Cardiac/chemically induced , Lanatosides/poisoning , Nifedipine/pharmacology , Pyridines/pharmacology , Animals , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/prevention & control , Blood Pressure/drug effects , Cats , Female , Heart Rate/drug effects , Lanatosides/antagonists & inhibitors , Male , Nifedipine/therapeutic useSubject(s)
Apomorphine/pharmacology , Arrhythmias, Cardiac/prevention & control , Cardiovascular System/drug effects , Deslanoside/antagonists & inhibitors , Lanatosides/antagonists & inhibitors , Animals , Arrhythmias, Cardiac/chemically induced , Blood Pressure/drug effects , Brain/drug effects , Cats , Decerebrate State , Haloperidol/pharmacology , Heart/drug effects , Heart Conduction System/drug effects , Heart Rate/drug effects , Piribedil/pharmacology , Propantheline/pharmacology , Receptors, Dopamine/drug effectsABSTRACT
The effect of ganglionic blockade on cardiotoxicity induced by deslanoside (25 mug/kg i.v. at 15-minute intervals) was evaluated in Dial-urethane anesthetized cats. Electrocardiogram, blood pressure and pre- and postganglionic cardiac sympathetic nerve recordings were monitored. When deslanoside was given to control animals, 150 +/- 8.2 and 179 +/- 11.9 mug/kg produced ventricular tachycardia and ventricular fibrillation, respectively. Pretreatment of cats with either hexamethonium or atropine alone did not influence the doses of deslanoside required to produce ventricular tachycardia or ventricular fibrillation. However, pretreatment with the combination of hexamethonium and atropine significantly increased the dose of deslanoside needed to produce ventricular tachycardia (181 +/- 12.3 mug/kg) and ventricular fibrillation (219 +/- 12.3 mug/kg). Furthermore, administration of atropine to hexamethonium-pretreated cats intoxicated with deslanoside decreased deslanoside-induced postganglionic nerve activity. These results indicate that blockade of both nicotinic and muscarinic ganglionic transmission is essential for a protective influence against cardiotoxicity induced by deslanoside.