UAMS Researchers Design antibody to PCP overdose

University of Arkansas for Medical Sciences
28-Oct-97

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Bonnie Brandsgaard
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UAMS Researchers Design antibody to PCP overdose

Little Rock, AR., October 28, 1997--With the deceivingly odd nickname of ÏAngel Dust,Ó young people disregard the terrible risks of phencyclidine abuse. They take PCP without being aware of its potentially dangerous and long-lasting effects, which include hallucinations, paranoia, violence and even comas. Currently, there is no clinically effective antidote for PCP overdose.

National statistics and media reports indicate young peopleÛfrom central Kansas City to west coast Los AngelesÛare being brought into emergency rooms after using PCP. Typically, they are out of control with no comprehension of their surroundings, perhaps because the drug prevents them from feeling pain, and it causes delusional thinking. As a result, they can be terribly dangerous to themselves as well as to others, including the healthcare professionals who take care of them. In addition, in up to 10% of the patients the drug can cause a coma, which can last for several days.

But, now PCP overdose may be reversible with a new antibody medical treatment, thanks to research at the University of Arkansas for Medical Sciences (UAMS), which is funded by the Medications Development Program at the National Institute on Drug Abuse.

UAMS scientists, headed by Dr. Michael Owens, a Professor in the College of Medicine, are developing an antibody-based therapy which can rapidly reverse the toxicity of phencyclidine.

Although the drug produces its effects at many sites of action within the brain, their preclinical studies show that the antibody can bring animals out of a severe drug-induced state in minutes. ÏIf our research continues to progress at its current rate, in the near future medical care for PCP abuse will include a medication that can rapidly reverses PCPÌs harmful effects. In the past most medical treatments for drug abuse have attempted to block effects of the drugs at their receptors in the brain. Our biotechnology-based therapy targets the drug, rather than the receptor. In fact, the antibody doesnÌt even enter the brain and it is still effective.Ó

Dr. Owens went on to say ÏSince PCP use can precipitate a latent psychosis, and result in a long-lasting dementia that closely resemble schizophrenia, we think it is important to get rid of the drug in the body as quickly as possible before it does too much permanent damage.Ó

Studies conducted by Shane Hardin, a M.D./Ph.D. graduate student in Dr. OwensÌ laboratory, show that the antibody therapy is effective not only against PCP but also against other drugs which are closely related to the structure of PCP. This is may be an important new medical approach since clandestine drug laboratories often produce a wide range of so-called Ïdesigner drugsÓ of abuse based on a known starting compound like PCP. The UAMS investigators have shown that a single Ïdesigner antibodiesÓ can be developed to treat the adverse effects caused by several different drugs with similar molecular structures. This recognition is analogous to the way we easily pick out the facial characteristics of people from the same family. Says Hardin, Ïthese studies could serve as a model for the development of antibody-based therapies for other classes of drugs and toxins.Ó

In a report, presented at the 1997 Neuroscience Conference in New Orleans on October 25-30, Dr. OwensÌ group presented their findings. He said, ÏThe focus of our research is to develop medications for treating drug abuse. Up until now there has been very little we could do for these patients except treat some of the symptoms and wait for them to get better on their own.Ó This medication was developed by the use of monoclonal antibodies, which were generated in tissue culture bioreactors without the need for live animals

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BACKGROUND
PCP was developed in 1959 as an anesthetic to alleviate pain and suffering during surgery. However, its development had to be discontinued in 1965 because it was found that patients often became agitated, delusional and irrational while recovering from anesthesia. Over the decades, its reputationÛas a drug for producing Ïbad tripsÓÛ fades and then resurfaces with each new generation of drug abusers. One of the reasons it continues to be a problem is that it is so cheap and it is often sold as an adulterate or substitute for other drugs of abuse.

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