NEW YORK (Reuters Health) - Serotonin receptor antagonists may be effective in preventing the spread of the human polyomavirus JCV in the central nervous system, and thereby avert the development or spread of progressive multifocal leukoencephalopathy (PML), according to research published in the November 19th issue of Science.
JCV is highly prevalent in the adult population, but leads to PML only in severely immunocompromised individuals, including patients with AIDS, senior author Dr. Walter J. Atwood told Reuters Health.
Dr. Atwood, a scientist at Brown University in Providence, Rhode Island, and his co-authors previously showed that the serotonin-dopamine inhibitors chlorpromazine and clozapine block JCV infection of glial cells. To further investigate, they tested other, more specific dopamine and serotonin receptor antagonists.
Dopamine-specific antagonists failed to block JCV infection in isolated glial cells. Only those with activity against 5HT2A or 5HT2C receptors, including serotonin, ketanserin and ritanserin, effectively prevented infection.
Antibodies to these two receptors also inhibited infection. Further proof that 5HT2A is a functional entry receptor for JCV was found when HeLa cells, normally impervious to JCV, could be infected following transfection with 5HT2A receptors.
“Most drugs that block these serotonin receptors are generally benign, they’re generic, and already approved by FDA, so we are in discussion with neurologists to investigate whether or not these compounds will be effective in preventing PML,” Dr. Atwood told Reuters Health.
“The drug cyproheptadine, which blocks 5HT2A receptors and is commonly used in AIDS patients as an appetite stimulant,” is one that clinicians may want to try, he added. Other options are serotonin receptor inhibitors used as antidepressants. Agents like chlorpromazine and clozapine are probably not practical because of their side effect profile.
“The question is, once the disease has developed, is it possible to treat it?” Dr. Atwood said. Patients “may be too far gone at that point.” But it is also possible that “AIDS patients could take such drugs prophylactically to prevent them from developing the disease in first place.”
Source: Science 2004;306:1380-1383. [ Google search on this article ]
MeSH Headings:Heterocyclic Compounds: Heterocyclic Compounds, 1-Ring: Heterocyclic Compounds, 2-Ring: Ketanserin: Membrane Proteins: Piperidines: Pyrimidinones: Quinazolines: Receptors, Cell Surface: Receptors, Serotonin: Ritanserin: AIDS-Related Opportunistic Infections: Receptors, Neurotransmitter: Receptors, Biogenic Amine: Chemicals and DrugsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
