Dihydrogenated ergot compounds bind with high affinity to GABAA receptor-associated Cl- ionophore.
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.
Tvrdeić
A
A
Ruder Bosković Institute, Department of Experimental Biology and Medicine, Zagreb, Croatia, Yugoslavia.
Pericić
D
D
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004087:Dihydroergotamine / Q000494:pharmacology; D004088:Dihydroergotoxine / Q000494:pharmacology; D004876:Ergot Alkaloids / Q000494:pharmacology*; D004879:Ergotamines / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007476:Ionophores; D051379:Mice; D008808:Mice, Inbred CBA; D011963:Receptors, GABA-A / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004876:Ergot Alkaloids; D004879:Ergotamines; D007476:Ionophores; D011963:Receptors, GABA-A; D004088:Dihydroergotoxine; D004087:Dihydroergotamine; D005680:gamma-Aminobutyric Acid; C037580:9,10-dihydroergosine; C046308:tert-butylbicyclo-2-benzoate