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
(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.