9-10-dihydroergosine and Seizures

The potential antidepressant dihydroergosine enhanced the convulsive properties of picrotoxin and bicuculline in rats and diminished them in mice. The possibility of dihydroergosine modulating species-dependently GABA/benzodiazepine receptors is suggested.

Topics: Animals; Antidepressive Agents; Bicuculline; Dose-Response Relationship, Drug; Drug Interactions; Ergotamines; Female; Male; Mice; Mice, Inbred CBA; Picrotoxin; Rats; Rats, Inbred Strains; Receptors, GABA-A; Seizures; Species Specificity

Dihydroergosine (50 and 100 mg/kg) enhanced the incidence of bicuculline (3 mg/kg)-induced convulsions in female rats, while 100 mg/kg of dihydroergosine given to female mice made 45% convulsive dose of bicuculline (2.5 mg/kg) to be subconvulsive. The same dose of dihydroergosine enhanced in mice the latency of bicuculline (4 mg/kg)-induced convulsions. Although, in in vitro experiments dihydroergosine showed very weak ability to prevent the binding of 3H-muscimol, the drug was able to diminish and to augment the IC50 of bicuculline and GABA when added to crude synaptosomal pellet of the rat and mouse brain respectively. Lower concentrations of dihydroergosine stimulated and higher inhibited 3H-TBOB binding to the crude synaptosomal pellet of the rat brain. In the preparation of mouse brain dihydroergosine produced only inhibition of 3H-TBOB binding. Only slight quantitative differences were observed in bicuculline-induced stimulation and in GABA- and diazepam-induced inhibition of 3H-TBOB binding between the two species. The results suggest that the opposite species-dependent effects of dihydroergosine on bicuculline-induced convulsions are due to the ability of this drug to modulate species-dependently the benzodiazepine/GABA receptor chloride channel complex.

Topics: Animals; Bicuculline; Brain; Chloride Channels; Diazepam; Ergotamines; Female; gamma-Aminobutyric Acid; In Vitro Techniques; Membrane Proteins; Mice; Mice, Inbred CBA; Muscimol; Rats; Rats, Inbred Strains; Receptors, GABA-A; Seizures; Species Specificity