Original scientific paper
Effect of Ergot Alkaloids on 3H-Flunitrazepam Binding to Mouse Brain GABAA Receptors
Ante Tvrdeić
Danka Peričić
Abstract
In vitro effects of dihydroergotoxine, dihydroergosine, dihydroergotamine, -dihydroergocriptine
(ergot alkaloids), diazepam, methyl--Carboline-3-carboxilate (-CCM),
flumazenil (benzodiazepines), -amino butyric acid (GABA) and thiopental (barbiturate)
were studied on mouse brain (cerebrum minus cerebral cortex) benzodiazepine
binding sites labeled with 3H-flunitrazepam. Specific, high affinity (affinity constant,
Kd = 57.7 8.6 nM) binding sites for 3H-flunitrazepam on mouse brain membranes were
identified. All benzodiazepine drugs inhibited 3H-flunitrazepam binding with nanomolar
potencies. In contrast to benzodiazepines, all ergot drugs, GABA and thiopental produced
an enhancement of 3H-flunitrazepam binding to its binding site at the GABAA receptor
of the mouse brain. The rank order of potency was: neurotransmitter (GABA) >
dihydroergotoxine > thiopental > -dihydroergocriptine > dihydroergosine > dihydroergotamine.
The results suggest that dihydrogenated ergot derivatives do not bind to the
brain benzodiazepine binding sites labeled with 3H-flunitrazepam. However, an enhancement
of 3H-flunitrazepam binding by all ergot drugs tested, clearly identifies an allosteric
interaction with the benzodiazepine binding sites of GABAA receptors.
Keywords
ergot drugs; 3H-flunitrazepam; GABAA; mouse
Hrčak ID:
28134
URI
Publication date:
26.6.2003.
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