One approach is to search for compounds with a slower onset of action than cocaine that produce less euphoria and have a longer duration of action. Another is to design very slow onset compounds that would probably produce only subtle effects. Some of these compounds may enter the brain very slowly, but once they are there, they may hang onto the receptors for a long time. Others may be compounds that are slowly activated and gradually accumulate on brain receptors, he says. It is also possible to modulate a compound's onset of action pharmaceutically by manipulating its rate of absorption by the body with transdermal patches or controlled-release forms of administration, Dr. Vocci points out.
Many complex factors affect a compound's rate of action in the human body.
These factors include the compound's structure and properties, how quickly the body absorbs it and transports it to the brain, and how rapidly it crosses the blood-brain barrier and binds to a sufficient number of targeted brain sites called receptors to produce its effects. Because the method of administering a drug affects a number of these factors, it can play a major role in the drug's rate of action and abuse liability. By using different methods of administering a compound, scientists can slow its rate of action and produce milder effects that may substitute for the stronger effects of an abused substance. Such a compound may be an effective medication for patients in treatment. However, unlike smoking a cigarette, which delivers an almost instantaneous burst of nicotine-laden blood to the brain, administering nicotine through a patch affixed to the skin slows its rate of action and produces more sustained, lower peak levels of nicotine in the blood.