!; Pharmacology Biochemistry & Behavior, Vol..38. pp. 135-139. _ Pergamon Press pie, 1991. Printed in the U.S.A.

nted in the U.S.A. 0091-3057/91 $3.00 + .00

5-Iodo-2-Aminoindan, a Nonneurotoxic
Analogue of p-Iodoamphetamine

DAVID E. NICHOLS, t MICHAEL P. JOHNSON AND ROBERT OBERLENDER

Department of Medicinal ChemistD, and Pharmacognosy and Department of Pharmacology and Toxicology ,.
School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafaye?te, IN 47907

Received 16 August 1990

'_ NICHOLS, D. E., M. P. JOHNSON AND R. OBERLENDER. 5-1odo-2-aminoindan, a nonneurotoxic analogue °fp-iodoamphet-
amine. PHARMACOL BIOCHEM BEHAV 38(1) 135-139, 1991.--A rigid analogue, 5-iodo--2-aminoindau (5-IAI), of the sero-
tonin neumtoxic halogenated amphetamine p-iodoamphetamine (PIA) was pharmacologically evaluated for production of serotonin
neurotoxiclty, A comparison was also made between 5-1Al and PIA in the two-lever drug di_rimination paradigm in rats trained to
di,scriminate saline from 3,4-methylenedioxymethamphetamine (MDMA) or saline Pfrom the a-ethyl hot:/_slogue of MDMA, MBDB.
PIA and 5-1AI were both behaviorally active, and fully substituted in both groups of animals, but were considerably less potent than
p-chloroamphetamlne (PCA). PIA had about twice the potency of PCA as an inhibitor of [3H]-5-HT uptake in rat brain cortical syn- _¢
aptosomes, while 5-1AI was only about 75% as potent as PCA in this assay. A single 40 rog/kg dose of PIA resulted in a 40% re.

duction of 5-HT and 5-HIAA levels and in the number of 5-HT uptake sites in rat cortex at fine week sacrifice. The same dose of
5-IAI with one week sacrifice led to about a 15% deci'ease in 5-HIAA levels and number of 5.HT uptake sites, but only the latter
was statistically significant. In rat hippocampus, PIA gave significant decreases in all _rotonin markers examined, while 5-IAI
slightly but significantly decreased only 5-HT levels. Neither compound produced any change in catecholamioe or catecbolamine
metabolite levels. The results confirm earlier reports of the selective serotonin neurotoxicity of PIA, which is less severe than that
of PCA, and also demonstrate that its rigid analogue 5-IAI does not appear to cause significant serotonin deficits in the rat.

p-todoamphetamine(PIA) p-Chlomamphetamine (PCA) Serotonin Neurotoxicity HPLC-EC Iodoaminoiodan

IT is now well established that p-chloroamphetamine (PCA) pro- p-fiuoro, p°bromo and more recently p-iodoamphetamine (3,7).
:_ duces a short-term reversible and a long-term irreversible deple- p-lodoamphetamine (PIA) resembled PCA in many respects, in-
tion of serotonin (5-HT)and 5-hydroxyindoleacetic acid (5-HIAA) cluding its tissue distribution, half-life, and ability to inhibit
i (5, 6, 10). More recent work has suggested that the long-term ir- [t4C]-5-HT uptake and block degradation of 5-HT by mitochon-

fine axons depletion

originatingof from
5-HT the dorsal
to araphe nucleus (13). In ad- acteristic of PCA alsb occurred with PlA and, as with
! reversible is due selective degeneration of drial monoamine oxidase. The long-term depletion of PCA,
5-HT these
char-
dition to the extensive work with PCA itself, certain studies have long-term deficits were prevented by pretreatment with the 5-HT
reported on both the short-term and long-term effects of structural uptake inhibitor, fluoxetine (7).
analogues of PCA, For example, the conformationally rigid aaa- The present report describes pharmacological data for a rigid
logue '6-chloro-2-aminotetralin retains acute serotonergic actions, analogue of PlA, 5-iodo-2-aminoindan (5-1AI; Fig. 1). It was
but does not cause long-term irreversible depletion of 5-HT sim-

· ilar laboratory
our to PCA (4). These results
(unpublished have The
results). beenloss
recently confirmed
of serotonin neuro-in

amphetamines was further illustrated when applied to 3,4-meth- NH 2

toxicity following rigidification of the side chain of substituted }__'cJ_rf_
- }} - NH2 J_.._/_)'_J_x
_[,
ylenedioxy-substituted compounds. Specifically, 3,4-methylene- i.._ 2J CH3 I" _
dioxyamphetamine (MDA) causes serotonin neurotoxicity similar
to PCA (18), but the rigid analogues, 5,6-methylenedioxy-2-ami-
noindan (MDAI) and 6.7-methylenedioxy-2-aminotetralin (MDAT) PlA 5-IAI
i do not appear to.possess this action (14).
i[_ i Another series of structural analogues of PCA results when
_ _ the chlorine atom is replaced to give other p-halogenated amphet- FIG, 1. Structures of p-iodoamphetamine (PIA) and 5-iodo-2-aminoindan
i amines. Earlier studies have included comparisons of p-chloro, (5-IAI).

t
! _Requests for reprints should be addressed to David E. Nichols, Department of Medicinal Chemistry and Pharmacognosy, Purdue University, West
; _ Lafayette, tN 47907.

135 9 9_ '_'
 136 NICHOLS, JOHNSON AND OBERLENDER

_XBL_ lA
SUBSTITUTION IN MDMA-TRAINED ANIMALS

Dose EDso§
Drug (mg/kg;
jxM/kg) N* D'J' %SDL_ mg/kg IxM/kg

PCA 0.17¶ 0.84

(mol.wt. = 207) (0.09-0.32) (0.46--1.55)
PIA 0.5; 1.68 8 0 13 1.16 3.91
(mol.wt. = 298) 1.0; 3.36 8 0 _. 38 (0.78-1.74) (2.61-5.85)
1.5; 5.04 9 1 50
2.0; 6.72 9 I 88
5-1AI 0.125;0.42 9 0 22 0.65, 2.19
(mol.wt.=296) 0.25; 0.85 9 1 38 (0.25-1.70) (0.83-5.75)
0.5; 1.69 9 I 50
1.0; 3.38 8 0 50
2.0; 6.77 lO 2 50
3.0; 10.14 I1 3 88

envisioned that 5-IAI might retain the short-term actions of PlA
but lack the long-term neurodegeneration associated with PIA and
PCA. In addition, it was anticipated that radiolabelled [_25I]-PIA
[as suggested by Fuller et al. (7)], and [J2Sl]-5-lAI might be use-
ful to visualize binding sites in brain utilizing autoradiography
techniques,
METHOD
Materials
PIA.HCI, 5-IAI.HCI, MDMA.HCI and (+)-MBDB'HCI were
} synthesized in our laboratories using standard procedures (15).
_ All spectral and elemental analyses were consistent with the ex-
pected structures. Fluoxetine. HCl was kindly provided by Eli Lilly
laboratories (Indianapolis, IN). The HPLC-EC standards were
purchased from Sigma Chemical Co. (St. Louis, MO). [3H]-Par-
oxetine was purchased from New England Nuclear (Boston, MA)
i at a specific activity of 28.8 Ci/mmol. [3H]-5-HT was purchased
from Amersham (Arlington Heights, IL) at a specific activity of
9.3 Ci/mmol.
Animals
Male Sprague-Dawley rats (175 to 200 g) were used in all ex-
periments. Animals were individually caged in a temperature-
controlled room with a 12/12 h lighting schedule. Rats used in
neurotoxicity tests were given food and water ad lib, while rats
used for drug discrimination testing were given free access to
water and enough food to maintain them at about 80% of their
free-feeding weight. Animal brain dissections were done over
ice and the areas removed according to the procedure of Glowin-
ski and Iversen (8). Brain areas from each hemisphere were sep-
arated and frozen with liquid nitrogen before storing at -70°C
untilassay,
Drug Discrimination
The procedures and equipment employed have been described
in detail (17). Briefly, rats were trained to discriminate either
MDMA'HCI (1.75 mg/kg) or S-MBDB.HCI (16) (1.75 mg/kg)
from saline using a fixed ratio (FR-50) schedule of food rein-
forcement. Intraperitoneal injections were given 30 min prior to
sessions. Test sessions were separated by at least one drug and
one saline maintenance session. Test sessions ended after 5 rain
or when 50 responses we,e made on either lever, whichever came
first. If 5 min passed without the rat emitting 50 responses, the
animal was scored as disrupted and was not used in the calcula-
tion of the EDr,o. Animals were not tested if, in the preceding
maintenancesessions,the rat gave less than 85% respondingon
the correct lever prior to the first reinforcement. Following the
procedure of Colpaert et al. (2), test data were discarded and the
condition later retested if the rat responded incorrectly in either of
the following two maintenance sessions. At least eight rats were
tested at each dose.
HPLC With Electrochemical Detection
The frontal cortex or hippocampal regions from one hemi-
sphere in each rat were weighed, and homogenized in 0.5 ml of
0.4 N HC104 containing 0.05% Na2EDTA, and 0.1% Na2S20 _
using a motor-driven teflon pestle and Eppendorf 1.5 ml centrif-
ugation tubes. An internal standard of 3-(3,4-dihydroxyphenyl)
propionic acid (100 ng/ml, DHPPA) was used. The samples were
centrifuged fro: 4 min at 14,000× g and the supematant was as-
sayed for the levels of NE, DA, DOPAC, HVA, 5-HT, and 5-
HIAA. The HPLC-EC system consisted of a Brownlee CI8
analytical cartridge column (Anspec, Ann Arbor, MI), a refriger-
ated autosampler (TosoHass, Philadelphia, PA) and a Model 400
EG&G Princeton electrochemical detector (Princeton, NJ). The
dual electrode potentials were set at E l = - 200 mV and E, -- 850
mV versus the Ag/AgCI reference electrode. The mobile phase
consisted of 0.05 M NaHePO 4, 0.03 M citric acid, 0. I mM
Na2EDTA, 0.034% sodium octyl sulfate and 25% methanol (pH =
2.75), at a flow rate of 1.0 ml/min. The monoamine and metab-
olite levels were quantitated using the Dynamax Method Manager
software(Rainin,Woburn, MA) with an Apple MacintoshSE
computer.
[SH]-Paroxetine Binding
The procedure of Habert et al. (9) as adopted by Battaglia et
al. (1) was employed with minor modifications. Briefly, the fron-
tal cortex and hippocampus from one hemisphere were thawed.
weighed, and homogenized with a Brinkman polytron (setting 6.
2 x 20 s) in 5 ml of 50 mM Tris HCI containing 120 mM NaCI
 IODOAMINOINDAN 137

i TABLE lB
SUBSTITUTION IN ( + )-MBDB-TRAINEDANIMALS

Dose EDco§
Drug (rog/kg; ixM/kg) N* D'I' %SDL:I: mg/kg g,M/kg

PCA 0.17¶ 0.82

(0.10-O.28) (0.50-1.36)

PIA 0.25; 0.84 8 0 25 0.54 1.81

0.50; 1.68 9 I 25 (0.35--0.82) 1.18--2.74)
0.75; 2.52 10 2 63
1.00; 3.36 8 0 88 ,.
5-1Al 0.25; 0.85 9 I 0 0.79 _ 2.67
0.50; 1.69 8 0 50 (0.42-1.48) (1.43-5.00)
1.00;3.38 10 2 63
2.00;6.77 12 4 75
2.50:8.46 10 2 88 ',

Animals were trained to discriminate either MDMA or (+)-MBDB from saline using a two-lever drug dis-
crimination paradigm. At least eight rats were tested at each dose as indicated. The EDCo values for substitu-
tion in MDMA-trained (Table lA) and (+)-MBDB-trained (Table lB) animals were calculated according to
the method of Litchfield and Wilcoxon (12). ,
*N =Total number of rats tested. -_
tD = Number of disruptions (50 presses not completed in 5 rain).
$Percentage of responding (N-D) rats selecting the drug lever, t
§95% confidence limits in parentheses.
¶Values taken from Johnson et al. (I l). ,

and 5 mM KCI (pH = 7.4). The homogenates were centrifuged at was added, and the vials were allowed to sit overnight before
30,000 x g for 10 min, and washed in the same buffer and recen- counting at an efficiency of 54%.
i trifuged. The resulting pellet was resuspended and chilled on ice
until assay. Uptake Inhibition of [_HI-5-HT
The binding of a single saturating concentration (1 nM) of
[3H]-paroxetine in tissue homogenates was examined. Specific The procedure of Steele et al. (19) was employed with minor
binding was defined as that displaceable with I txM fluoxetine, modifications. Briefly, the whole cortex was homogenized in 15
Incubations commenced with the addition of tissue to the buffer volumes of 0.32 M sucrose With a glass mortar and motor-driven
described above to give a total volume of 2 mi. The tubes were teflon pestle. The homogenate was then centrifuged at 11300x g
equilibrated at 24°C for 1 h before filtering through GF/C' filters for 10 min at 4°C and the resulting supematant centrifuged at
presoaked with 0.05% PEI, using a Brandel Cell Harvestor 17,000xg for 10 min. The resulting pellet was resuspended in
(Gaithersburg, MD). The tubes were then rapidly washed twice the same volume of s0crose and placed.in an ice bath until used.
with ice-cold buffer. The filters were allowed to air dry and were A 200 $xl aliquot of the above tissue homogenate was added
then placed in scintillation vials, I0 mi of scintillation cocktail to 1.65 mi ofOe-saturated Krebs-Henseleit buffer (I 18 mM NaCl,
4.8 mM KC1, 1.3 mM CaCl2, 1.2 mM KHePO 4, 1,2 mM
: MgSO4, 25 mM NaHCO3, 10 mM glucose, 0.06 mM ascorbic
acid and 0.03 mM Na2EDTA), 50 $xl drug, and 50 gl pargyline
TABLE 2 (final concentration, 1 IxM). Following a 5-rain preincubation at
UPTAKE INHIBITION OF [3HI-5-HT 37°C, [3HI-5-HT was added in 50 $xl aliquots to give a final con-
centration of 10 nM. Tubes were allowed to equilibrate for an
additional 5 rain at 37°C before cooling in an ice bath. The syn-
lCso (nM)
aptosomes were collected by filtering through Whatman GF/B
filters utilizing a Brandel cell harvestor (Gaithersburg, MD). The
FCA 184 +- 12 filters were washed twice with 5 ml of cold buffer and allowed
PlA 82 _ 8* to air dry before preparing the samples for counting as described
5-1Al 241 _ 21'I' above.

The inhibition of [JH]-5-HT uptake was examined in rat brain cortical

i synaptosomes. The IC_o values represent the mean ± S.E.M. of three to Statistical Analysis
four separate experiments. Each experiment utilized 5 or 6 concentra-
tions, nm in triplicate, on the linear portion of the dose-response curve. In drug discrimination experiments, EDso values and 95%
*Indicates significantly different from PCA (p<0.05, ANOVA followed confidence intervals were determined from quantal dose-response
by post hoc comparison), curves according to the procedure of Litchfield and Wilcoxon
tlndicates significantly different from PIA (p<0.05, ANOVA followed (12). The ICao values for uptake inhibition were calculated from
by post hoc comparison), a graded dose-response curve by the method of Tallarida and
!_,,, 138 NICHOLS,
JOHNSON
ANDOBERLENDER

A. Ez3 $olin_ Murray (20). For neurochemical analyses, comparisons between

EZa P_ treatment groups utilized an analysis of variance followed by a
5-IN
post hoc comparison, as embodied in the EPISTAT software
!00
, (EPISTAT Services. Richardson, TX).

'_ 80 RESULTSANDDISCUSSION
t-
O
o 60 Both PlA and 5-IAI were behaviorally active in the drug dis-
'E criminationparadigm.As seen in Table1, bothtest compounds
40 fully substituted in rats trained to discriminate MDMA or (+)-
MBDB from saline. Interestingly, 5-IAI is significantly less po-
5 m tentthanPIAat inhibiting the synaptosomal uptakeof [3H]-5-HT
20, in vitro (Table 2)'. In addition, PlA was significantly less potent
than PeA in MDMA-trained rats. Fuller et al. (7) have previouslY'
0 shownthat PIA is a lesspotent depictorof 5-HT and5-HIAA
5-HT 5-HIAA U )take than is PeA. This occurs despite the fact that PIA has equal or
Frontal Cortex greater potency than PCA in a number of in vitro assays. For ex-
ample, PlA is slightly more potent than PCA at inhibiting synap-
[3. E3 Sa,ne
PlA tosomal ['4C]-5-HT uptake (7). In our laboratory, PlA is a
· eZa 5-_ significantly more potent inhibitor Of synaptosomal uptake of
100- lower concentrations of [3H]-5-HT (Table 2). In addition, Fuller
· et al. (7) have repo_rtedthat PIA is substantiallymore potent than
ii. '_ 80 PCA as andan inhibitor of monoamine oxidase.
(7), Given the similar
_'_ .,., half-life distribution .of PlA and PCA the reason for the
_ c apparent discrepancy between the in viva and in vitro potencies
[i o 6o is not readily apparent.
!/_ll_ '_ As seen in Fig. 2, PIA caused a significant decrease in sero-
o 40 tonergic markers one week after a single 40 rog/kg (0.13 mmol/
kg) dose. This was a selective serotonergic effect since no changes
20 in NE, DA or their metabolites were seen with any drug treatment
(Table 3). As previously indicated (7), the relative neurotoxicity
o of PIA is substantially less than that of PCA. While PCA (0.05
5-HT 5-HIAA Uptake mmol/kg) causes a 75% reduction in serotonergic markers (I I),
0.13 retool/kg of PIA caused only a 40% reduction (Fig. I). Pre-
Hippocompus viously, 0.10 mmol/kg (30 mg/kg) of PlA has been reported to
cause a 20 to 30% reduction in 5-hydroxyindoles (7).
As anticipated, 5-IAI appears to be significantly less neuro-
FIG. 2. 40
Serotoninergic
mg/kg PIA,markers following acutedosing withsubcutaneously
PIA or 5-1AI. toxic than PIA (Fig. 2). Only slight decreases of serotonergic
Saline. or 40 rog/kg 5-IAI was injected
and animals were sacrificed one week later. Serotonin and 5-HIAA lev- markers (15% or less) were seen one week following a single 40
els were determined in frontal cortex (A) and hippocampal (B) areas us- rog/kg (0.13 mM/kg) SC dose of 5-IAI. The only statistically
lng HPLC-EC techniques. The number of uptake sites remaining was significant decreases were in the number of cortical uptake sites
determined by examining the ability of a saturatingconcentration of [3H]- and the hippocampal levels of 5-HT (Fig. 2). One could specu-
paroxetineto bind to tissue homogenates as described in the Method sec- late that higher doses might lead to significant decreases in all the
tion. Values arerepresented as the mean+ S.E.M. for n = 8. Saline control serotonergic parameters. However, a 40 rog/kg dose is already
values were as follows: cortical 5-HT, 366+_27; 5-HIAA, 296'-.27 pg! some 20- to 40-fold higher than a behaviorally active dose, and
mg wet wt.; uptake sites, 16.8'-.0.6 final/rog wet wt.; and hippocampal it has been our experience that doses of many amphetamine ana-
5-HT. 400 +-22; 5-HIAA, 558 +-18 pg/mg wet wt.; uptake sites 16.1 '4-1.1 logues greater than 40 mg/kg are approaching lethal levels. Inter-
fmbl/mg wet wt. estingly, we have found that similar doses of 6-chloro-2-
aminotetralin (0.17 mmol/kg) resulted in slight reductions

TABLE 3
CATECHOLAMINE AND METABOLITE LEVELS

Cortical
(pg/mg wet wt.)
Hippocampal
Treatment NE DA DOPAC HVA NE

Saline 508 __21 40 ___4 16 +-3 23 +-I 590 + 28

PIA 504 +- 29 36 -- 3 16 __ 3 20 _+2 547 +- 42
5-IAI 540 +- 22 47 4- 5 13 _+2 19 +- 1 557 +- 26

Saline, 40 rog/kg PIA, or 40 mg/kg 5-1Al was injected subcutaneously and animals
were sacrificed one week later. The frontal cortex and hippocampal areas were analyzed
for NE, DA, DOPAC, and HVA levels utilizing HPLC-EC techniques. Values are re-
ported as the mean +- S.E.M. for N= 8.
 IODOAMINOINDAN 139

in serotonergic markers at one week, while a statistically signifi- nificant serotonin deficits in the rat, presumably reflecting a re-
cant decrease only occurred with the number of hippocampal 5- duced potential to induce serotonin neuron degeneration.
HT uptake sites (unpublished results).
In conclusion, the results indicate that both PIA and 5-IAt are ACKNOWLEDGEMENTS
behaviorally active in rats. PIA also appears to cause the same
type of serotonJn neurotoxicity that occurs with PCA, although We thank Stewart Frescas for carrying out the syntbems of PIA'HCI
PlA is somewhat less potent in this respect. Third, at the doses and 5-1AI.HCI. This work was supported by USPHS Grant DA-04758
examined, the rigid analogue 5-IAI does not appear to cause sig- from the National Institute on Drug Abuse.

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 LETFERS TO THE EDITOR

listened to their own heartbeats, developed exquisitely sen- Kueny, 1980 unpublished manuscript). Greer described one
sitJve hearing and smell, or concentrated on their pain. case (out of 80) of a man with a prior history of panic attacks
Patients reported that their depersonalization and loss of self who experienced a recurrence of the symptoms after using
became more severe when they were not "allowed" pain MDMA; his symptoms resolved after he reentered psycho-
(becat,se of the narcotic administration). Four patients had therapy. Generally, subjects describe an increase in mood
had visual and auditory hallucinations (e.g., a deceased and in the ability tocommunicate in individual and conjoint
mother returning from the grave to sit at the bedside), but psychotherapy, and enhanced introspective ability.
retrospectively it was difficult to'tell whether these phenom- MDMA has a brief duration of action (4-6 hours), is
cna were directly related to the patient's being paralyzed or usually administered in a dose of 75-150 mg orally as an
if thcy were secondary to the delirium accompanying phys- adjunct to psychotherapy, and has acute side effects that are
ical illness, primarily sympathomimetic in nature.
The posttraumatic stress disorders were characterized by MDMA has been placed in schedule I (with heroin and
screaming nightmares, intrusive recollections, irritability, LSD) on an emergency basis by the U.S. Drug Enforcement
suspiciousness toward caretakers, anger at the hospital and Agency (DEA). This apparently was done because of the
consenting relatives, withdrawal from visitors, suppressed increasing frequency of street use and because of concerns
and shameful memories of "having gone crazy," and a that MDMA's chemical similarity to methylenedioxy-
reluctance to return for aftercare. Four patients had had amphetamine (MDA), another schedule I drug, bespoke
suicidal ideation without immediate intent; they linked this similarities in clinical effects. An unpublished manuscript
ideation to the depressive realization that they had the that described serotinergic terminal degeneration in the CNS
capacity to lose control of their minds. Only one patient was was quoted from by the DEA in making its decision.
grateful for what he considered a "lifesaving" procedure; the However, that study used MDA, not MDMA. Even in the
other five said they would rather die than go through it best of circumstances, establishing a direct causal relation-
ag_ml, ship between the use of a psychoactive drug and subsequent
The prevalence of panic during pancuronium administra- "adverse reactions" is quite difficult (3). Abuse of a drug of
tion and of iatrogenic posttraumatic stress disorder is un- unknown purity, strength, and contaminants, in combina-
known and requires further investigation. Based on our tion with any number of other drugs and alcohol, in unpre-
evaluation of these six patients, we suggest that diazepam be pared subjects with an unknown degree of psychopathology
generously prescribed during the procedure, that staff and in an uncontrolled setting is not a test of whether or not the
relatives continually touch and talk to the patients, that drug has any potential therapeutic use or even high potential
tape-recorded explanationsfrom staff and reassurances from for abuse.
family be played when more personal contact is not avail- A number of psychotherapists who use MDMA as an
able, and that, following the treatment, patients be assessed adjunct to their psychotherapeutic practice, as well as a
and, if necessary, treated for posttraumatic stress disorder, number of other concerned parties, have called on the DEA
Our six patients responded to the psychotherapeutic inter- for an administrative law hearing with regard to classifying
ventions described by Horowitz (1). MDMA as a schedule I substance. These hearings are now in
progress and will not be completed until next year, when a
final decision will be made.
REFERENCE We hope the furor in the media and legislatures that made
1. Horowitz MJ: Stress Response Syndromes. New York, Jason research with psychedelic compounds so difficult (if not
Aronson,1976 impossible) to pursue in the 1960s will not have the same
effect on further rational inquiry into the mechanisms of
SAMUEL W. PERRY, M.D. action and clinical utility of MDMA.
New York, N.Y.

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(2). Anecdotal clinical reports describe a lack of the disori- Common Misconceptions About the Mental Status
entation, ego disruption, perceptual distortions, and tran- Examination
sient psychotic states that can occur with the more powerful
psy&edelics, when MDMA is used in a controlledenviron- SIR:As examiners for part II of the American [loam of
meat with careful supervision (Greet, 1983 unpublished Psychiatry and Neurology examination, we have observed
manuscript; Downing, 1984 unpublished manuscript; yearafteryearthatcandidatesmisconstruetheintentofmany

Am ! Psychiatry 142:li, November 1985 1391