1. 3,4-Dihydroxy- and 3,4-methylenedioxy- phenanthrene-type alkaloids with high selectivity for D2 dopamine receptor.
- Author
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Moreno L, Cabedo N, Ivorra MD, Sanz MJ, Castel AL, Carmen Álvarez M, and Cortes D
- Subjects
- Animals, Corpus Striatum drug effects, Corpus Striatum metabolism, Humans, Parkinson Disease drug therapy, Rats, Schizophrenia drug therapy, Alkaloids chemistry, Alkaloids pharmacology, Phenanthrenes chemistry, Phenanthrenes pharmacology, Receptors, Dopamine D2 metabolism
- Abstract
Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new drugs acting at the dopamine receptors (DR) as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) can behave as selective D2 dopaminergic alkaloids. In the present study we have synthesized five aporphine compounds and five phenanthrene alkaloids and evaluated their potential dopaminergic activity. Binding studies on rat striatal membranes were used to evaluate their affinity and selectivity towards D1 and D2 DR. Phenanthrene type alkaloids, in particular the 3,4-dihydroxy- and 3,4-methylenedioxy derivatives, displayed high selectivity towards D2 DR. Therefore, they are potential candidates to be used in the treatment of schizophrenia (antagonists) or Parkinson's disease (agonists) due to their scarce D1 DR-associated side effects., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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