Pharmacology and Toxicology of Amphetamine and - Archives

377 Pages·2002·3.35 MB·English

Pharmacology
and Toxicology
of Amphetamine
and Related
Designer Drugs
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol Drug Abuse and Mental Health Administration
Pharmacology and Toxicology
of Amphetamine and Related
Designer Drugs
Editors:
Khursheed Asghar, Ph.D.
Division of Preclinical Research
National Institute on Drug Abuse
Errol De Souza, Ph.D.
Addiction Research Center
National Institute on Drug Abuse
NIDA Research Monograph 94
1989
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
Alcohol, Drug Abuse, and Mental Health Administration
National Institute on Drug Abuse
5600 Fishers Lane
Rockville, MD 20857
For sale by the Superintendent of Documents, U.S. Government Printing Office
Washington, DC 20402

Pharmacology and Toxicology
of Amphetamine and Related
Designer Drugs
ACKNOWLEDGMENT
This monograph is based upon papers and discussion from a technical
review on pharmacology and toxicology of amphetamine and related
designer drugs that took place on August 2 through 4, 1988, in Bethesda,
MD. The review meeting was sponsored by the Biomedical Branch,
Division of Preclinical Research, and the Addiction Research Center,
National Institute on Drug Abuse.
COPYRIGHT STATUS
The National Institute on Drug Abuse has obtained permission from the
copyright holders to reproduce certain previously published material as noted
in the text. Further reproduction of this copyrighted material is permitted
only as part of a reprinting of the entire publication or chapter. For any
other use, the copyright holder’s permission is required. All other matieral
in this volume except quoted passages from copyrighted sources is in the
public domain and may be used or reproduced without permission from the
Institute or the authors. Citation of the source is appreciated.
Opinions expressed in this volume are those of the authors and do not
necessarily reflect the opinions or official policy of the National Institute on
Drug Abuse or any other part of the U.S. Department of Health and Human
Services.
The U.S. Government does not endorse or favor any specific commercial
product or company. Trade, proprietary, or company names appearing in
this publication are used only because they are considered essential in the
context of the studies reported herein.
DHHS publication number (ADM)89-1640
Printed 1989
NIDA Research Monographs are indexed in the Index Medicus. They are
selectively included in the coverage of American Statistics Index,
Biosciences Information Service, Chemical Abstracts, Current Contents,
Psychological Abstracts, and Psychopharmacology Abstracts.
iv
Contents
Page
Preface ix
Structure-Activity Relationships of MDMA-Like Substances 1
David E. Nichols and Robert Oberlender
Self-Injection in Baboons of Amphetamines and Related
Designer Drugs 30
CA. Sannerud, J.V. Brady, and R.R. Griffiths
Stimulus Properties of Hallucinogenic
phenalkylamines and Related Designer Drugs:
Formulation of Structure-Activity Relationships 43
Richard A. Glennon
Amphetamines: Aggressive and Social Behavior 68
Klaus A. Miczek and Jennifer W. Tidey
Neurochemical Mechanisms Involved in
Behavioral Effects of Amphetamines and Related
Designer Drugs 101
Lisa H. Gold, Mark A. Geyer, and George F. Koob
Neuronal Actions of Amphetamine in the Rat Brain 127
Philip M. Groves, Lawrence J. Ryan, Marco Diana,
Stephen J. Young, and Lisa J. Fisher
v
Page
Methamphetamine and Related Drugs: Toxicity and
Resulting Behavioral Changes in Response to
Pharmacological Probes 146
Lewis S. Seiden and Mark S. Kleven
Role of Dopamine in the Neurotoxicity Induced
by Amphetamines and Related Designer Drugs . 161
James W. Gibb. Donna M. Stone, Michel Johnson,
and Glen R. Hanson
Acute and Long-Term Neurochemical Effects of
Methylenedioxymethamphetamine in the Rat 179
Christopher J. Schmidt
Effects of MDMA and MDA on Brain Serotonin Neurons:
Evidence from Neurochemical and Autoradiographic Studies 196
Errol B. De Souza and George Battaglia
Characterization of Brain Interactions With
Methylenedioxyamphetamine and
Methylenedioxymethamphetamine 223
Robert Zaczek, Stephen Hurt, Steven Culp, and
Errol B. De Souza
Pharmacologic profile of Amphetamine Derivatives at
Various Brain Recognition Sites: Selective Effects
on Serotonergic Systems 240
George Battaglia and Errol B. De Souza
Effects of Amphetamine Analogs on Central Nervous
System Neuropeptide Systems 259
Glen R. Hanson, Patricia Sonsalla, Anita Letter,
Kalpana M. Merchant, Michel Johnson, Lloyd Bush,
and James W. Gibb
Effects of Neurotoxic Amphetamines on Serotonergic
Neurons: Immunocytochemical Studies 270
Mark E. Molliver, Laura A. Mamounas, and
Mary Ann Wilson
Studies of MDMA-Induced Neurotoxicity in Nonhuman
Primates: A Basis for Evaluating Long-Term Effects
in Humans 306
George A. Ricaurte
vi
Page
Dose- and Time-Dependent Effects of Stimulants 323
Everett H. Ellinwood, Jr., and Tong H. Lee
Recommendations for Future Research on Amphetamines
and Related Designer Drugs 341
Ray W. Fuller
List of NIDA Research Monographs 358
vii

Preface
The abuse of amphetamines is of national concern from a public health
perspective. Review of this subject is timely and important, because the
problem of amphetamine-like drugs has recently been amplified by the
introduction of designer drugs in the illicit market. There has been an
increasing number of attempts by chemists in clandestine laboratories to
synthesize structurally altered congeners that might intensify the mood-
altering property of this class of compounds. While attention over the last
few decades has been centered on research related to amphetamine,
methamphetamine, and clinically prescribed amphetamine derivatives
including fenfluramine, recent attention has focused on a variety of
amphetamine-related designer drugs. These designer drugs include ring-
substituted derivatives of amphetamine and methamphetamine such as
3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymetham-
phetamine (MDMA “ecstasy”), respectively. MDMA has been the focus of
a great deal of recent attention, since it represents one of a number of
“designer drugs” that is being increasingly abused among certain segments
of the population, especially among college students. This popularity is
ascribed to the drugs’ mixed central nervous system (CNS) stimulant and
hallucinogenic effects. Furthermore, MDMA has been the subject of recent
scientific and legal debate, as several psychiatrists have reported that
MDMA may “enhance emotions” and “feelings of empathy” and thus serve
as an adjunct in psychotherapy. While the psychotherapeutic usefulness of
this drug remains to be determined, a great deal of research has been
carried out on the abuse liability, behavioral effects, and neurotoxic effects
of the amphetamine-related designer drugs.
A technical review meeting entitled “Pharmacology and Toxicology of
Amphetamine and Related Designer Drugs” was held at the National
Institutes of Health on August 2-4, 1988. The purpose of the technical
review was to bring together scientists who have been carrying out research
in the area to (1) summarize the research findings, (2) understand the
neuronal mechanisms through which the amphetamines produce their effects,
and (3) develop a consensus regarding future directions that may lead to
better characterization of the effects of these drugs on various physiological
parameters. An understanding of the mechanisms is critical to the
development of therapeutic approaches for the treatment of intoxication,
addiction, and adverse effects. The proceedings of this meeting are
presented in the following chapters.
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