F. Ivy Carroll, Ph.D.

 

Dr. F. Ivy Carroll received the B.S. degree in chemistry from Auburn University in 1957 and was awarded the Ph.D. in chemistry by the University of North Carolina at Chapel Hill in 1961. He joined the research staff of the Research Triangle Institute as a Research Chemist and rose steadily to the position of Vice President of the Chemistry and Life Sciences Group, a position he held from 1996 to 2001. Dr. Carroll is presently Director of the Center for Organic and Medicinal Chemistry, a position he held since 1975, and is a Distinguished Fellow for Medicinal Chemistry (a position equivalent to Vice President).

Dr. Carroll is a member of the American Chemical Society (ACS); a fellow of the American Association for the Advancement of Science (AAAS), the American Association of Pharmaceutical Science (AAPS), the Royal Society of Chemistry (RSC), and the College on Problems of Drug Dependence (CPDD); and the honor societies, Sigma Xi and Phi Lambda Upsilon. His other professional and scientific activities include service on the Long-Range Planning Committee of the Medicinal Chemistry Section of the ACS and two terms of service on the ACS Offices and Awards Committee (Chairman for the last term). Dr. Carroll was a member of the Biochemistry Study Section of the National Institute on Drug Abuse Review Committee for four years; a member of the Molecular, Cellular, and Chemical Neurobiology Research Review Committee for two years; and a member of the Medications Development Division Review Committee of the National Institute on Drug Abuse for four years (Chairman for two years). He is presently a member of the NIH Molecular Neuropharmacology and Signaling Study Section. Dr. Carroll served on the Editorial Advisory Board of the Journal of Medicinal Chemistry from 1995 to 1999. He is presently the Medicinal Chemistry Section Editor for Drug Development Research, and is on the advisory boards of several other journals.

Dr. Carroll has made significant contributions to anti-cancer, anti-radiation, and anti-malarial research; however, his more recent studies have been directed mainly to drug abuse and central nervous system research. A major thrust of his research has involved the synthesis and pharmacological characterization of the 3-phenyltropane class of compounds. These compounds have had tremendous impact as tools to assist in establishing the biochemical mechanism of action of cocaine. The longer-term goal of this research was the identification and development of treatment drugs for cocaine addiction. This effort identified the dopamine transporter-selective analog, 3ß-(4'-chlorophenyl)-2ß-[3-(4’-methylphenyl)isoxazol-5-yl]tropane (RTI-336), as a pharmacotherapy for treatment of cocaine abuse. Preclinical studies have been completed, and the IND will be submitted in early 2008.

The 3-phenyltropane research has also led to the development of 3ß-(4-iodophenyl)tropane-2ß-carboxylic acid methyl ester (RTI-55). The radioisotopically labeled forms of RTI-55 have found commercial applications. [125I]RTI-55 is highly useful for biochemical studies of monoamine transporters and is presently marketed by Perkin Elmer. [123I]RTI-55 (Dopascan, Iometopane), also developed by Dr. Carroll, is a single photon emission computed tomography (SPECT) imaging ligand used as a diagnostic agent for Parkinson's disease. Thousands of patients have been diagnosed in the US, European countries, Japan, Korea, Taiwan, and Scandinavian countries. [123I]RTI-55 has also been heavily used as a clinical tool to study drug abuse patients. Dr. Carroll has 22 publications and seven patents devoted solely to RTI-55.

Dr. Carroll’s more recent research has been directed toward the study of opioid and nicotinic receptors. Most significantly, the studies have discovered JDTic, a potent and kappa opioid receptor selective antagonist. JDTic is the only small molecule kappa opioid selective antagonist not derived from the morphine-like structure, and JDTic is the only orally active kappa opioid receptor antagonist. Orally administered JDTic is active in the stress-induced cocaine relapse rat model and is also active in the rat forced-swim anti-depression model and in anxiolytic tests in rats. Preclinical studies are well on the way for IND submission for JDTic. In addition, Dr. Carroll’s opioid receptor research has lead to the development of four new structural types of opioid receptor pure antagonists, new structural types of opioid inverse agonists, and a novel structural type of opioid agonist.

The nicotinic research has provided [125I]iodo-MLA, which is the most selective ?7-nicotine receptor radioligand presently available, and 2-fluoro-(4-nitrophenyl)deschloro¬epibatidine (4-nitro-PFEB), which is the most potent and α4ß2 selective, competitive antagonist presently available. A number of other compounds have also been developed that serve as pharmacological tools to characterize the behavioral properties resulting from interaction with nicotinic receptors. Dr. Carroll's research efforts showed that (2S,3S)-hydroxybupropion, a major bupropion metabolite, is an α4ß2 AChR antagonist and, thus, may contribute to bupropion’s smoking cessation activity.

Dr. Carroll's research is documented in 393 peer-reviewed publications, 32 book chapters, and 36 patents. Ninety postdoctoral fellows have been trained by Dr. Carroll.

Awards and honors recognizing Dr. Carroll’s research accomplishments include: the 1993 Distinguished Lecturer award from the North Carolina Section of the American Chemical Society, the 2000 Southern Chemist Award from the Memphis Section of the American Chemical Society, the 2001 Herty Award from the Georgia Section of the American Chemical Society, the 2002 American Chemical Society Medicinal Chemistry Award, the Research Triangle Institute 2001 Margaret E. Knox Excellence Award, the 2006 Nathan B. Eddy Award from the College on Problems of Drug Dependence, and the 2006 Research Achievement Award in Drug Design and Discovery from the American Association of Pharmaceutical Scientists. The National Institute on Drug Abuse honored Dr. Carroll with the 1993 Pacesetter award and the 1996 MERIT award for his research on the biochemical mechanisms of the action of cocaine.