Sunday, March 14, 2010
The Cocaine Conundrum
Effective treatment remains elusive.
For addiction to cocaine, amphetamine, and other stimulants, the treatment picture has been complicated by the lack of any truly significant anti-craving medications. (See post, “No Pill for Stimulant Addiction"). The National Institute on Drug Abuse (NIDA) has yet to approve any medications for the treatment of either cocaine or amphetamine addiction.
Take the case of cocaine. Partly the problem stems from the direct effect cocaine has on dopamine transmission. The hunt for a pharmaceutical approach to blunt that effect is complicated by the problematic nature of dopamine receptors. Dopamine antagonist drugs like the antipsychotic drug haloperidol do not always block the stimulant rush. And their side effects, such as lethargy, emotional blunting, and tardive dyskinesia, make them unsuitable for ongoing addiction therapy. Conversely, some drugs that act as dopamine agonists turn out to be addictive in their own right. Many designer drugs are like that.
Because of all this, different approaches may be needed. The direct ride to the pleasure pathway provided by stimulants makes it difficult to tamper selectively with their effects. An antibody that would reduce cocaine consumption and sop up cocaine molecules in the brain, a kind of vaccine against cocaine, is one approach being pursued (See post, “Cocaine Vaccine Hits Snag”).
But other avenues of attack are being exploited. Scientists in NIDA’s Intramural Research Program are testing compounds that target certain proteins known as dopamine transporters. Transporters move dopamine molecules in and out of the synaptic gap between neurons in the brain. Interfering with that transportation system is another way of altering dopamine uptake, and it represents one active avenue of approach to the treatment of cocaine addiction.
The researchers tested Benztropine Mesylate (BZT), brand name Cogentin, one of a class of drugs known as anticholinergic suppressants commonly used in the management of Parkinson’s disease. What exactly does benztropine do? It possesses both anticholinergic (acetylcholine-blocking) and antihistaminic effects. It has chemical similarities to atropine, which is used for Parkinson’s and for heart disease.
To begin with, the researchers wanted to establish that benztropine itself is non-addictive. By substituting different BZT analogs for cocaine during self-administration testing on addicted rats, “two of the three BZT analogs that were tested significantly reduced drug self-administration… which indicates that those BZT analogs themselves have low potential for abuse.”
Next, the cocaine-addicted rats were given different BZT analogs before they got their cocaine. “When given before rats had access to cocaine in the self-administration chambers,” the researchers reported in the Journal of Pharmacology and Experimental Therapeutics, “two BZT analogs also significantly reduced the number of times the rats would press a lever to receive cocaine.” Monoamine uptake inhibitors were used as a control. The authors conclude that “these compounds are promising candidates for the development of medications for cocaine addiction.”
Hiranita, T., Soto, P., Newman, A., & Katz, J. (2009). Assessment of Reinforcing Effects of Benztropine Analogs and Their Effects on Cocaine Self-Administration in Rats: Comparisons with Monoamine Uptake Inhibitors Journal of Pharmacology and Experimental Therapeutics, 329 (2), 677-686 DOI: 10.1124/jpet.108.145813
Photo credit: http://www.drugabuse.gov