9-10-dihydroergosine and tert-butylbicyclo-2-benzoate

Dihydroergosine enhanced [3H]TBOB binding to the crude synaptosomal membranes prepared from the whole rat brain and human frontal cortex. Higher concentrations of the same drug inhibited [3H]TBOB binding in the preparations obtained from the whole mouse brain and bovine frontal cortex. Bicuculline-induced enhancement and GABA- or diazepam-induced inhibition of [3H]TBOB binding were similar in the four species examined. The results indicate that dihydroergosine modulates species-dependently GABA/benzodiazepine receptors.

Topics: Animals; Brain; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cattle; Cerebral Cortex; Ergotamines; Female; Humans; In Vitro Techniques; Mice; Mice, Inbred Strains; Middle Aged; Rats; Rats, Wistar; Receptors, GABA-A; Species Specificity; Synaptic Membranes; Synaptosomes

The binding of t-[3H]butylbicycloorthobenzoate ([3H]TBOB) to crude synaptosomal membranes of the mouse brain (cerebrum minus cortex) in the presence of dihydroergotoxine, dihydroergosine, dihydroergotamine and gamma-aminobutyric acid (GABA) was studied in vitro. [3H]TBOB binding was inhibited by all drugs used. The rank order of potency was dihydroergotoxine greater than GABA greater than dihydroergosine greater than dihydroergotamine. This suggests that dihydrogenated ergot compounds, especially dihydroergotoxine, possess appreciable binding activity (comparable to that of benzodiazepines and barbiturates) at the GABAA receptor-associated C1- ionophore.

Topics: Animals; Brain; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Dihydroergotamine; Dihydroergotoxine; Ergot Alkaloids; Ergotamines; Female; gamma-Aminobutyric Acid; In Vitro Techniques; Ionophores; Mice; Mice, Inbred CBA; Receptors, GABA-A; Synaptosomes