AMPT-induced monoamine depletion in humans: evaluation of two alternative [123I]IBZM SPECT procedures.
OBJECTIVE
Acute monoamine depletion paradigms using alpha-methyl-para-tyrosine (AMPT) combined with single photon emission computed tomography (SPECT) have been used successfully to evaluate disturbances in central dopaminergic neurotransmission. However, severe side effects due to relatively high doses (4,500 to 8,000 mg) of AMPT have been reasons for study withdrawal. Thus, we assessed the effectiveness and tolerability of two alternative procedures, using lower doses of AMPT.


METHODS
Six healthy subjects underwent three measurements of striatal dopamine D(2) receptor (D(2)R)-binding potential (BP(ND)) with SPECT and the selective radiolabeled D(2)R antagonist [(123)I]IBZM. All subjects were scanned in the absence of pharmacological intervention (baseline) and after two different depletion procedures. In the first depletion session, over 6 h, subjects were administered 1,500 mg of AMPT before scanning. In the second depletion session, over 25 h, subjects were administered 40 mg AMPT/kg body weight. We also administered the Subjective Well-being Under Neuroleptic Treatment Scale, a self-report instrument designed to measure the subjective experience of patients on neuroleptic medication.


RESULTS
We found no change of mean D(2)R BP(ND) after the first and short AMPT challenge compared to the baseline. However, we found a significant increase in striatal D(2)R BP(ND) binding after the AMPT challenge adjusted for bodyweight compared to both other regimen. Although subjective well-being worsened after the prolonged AMPT challenge, no severe side effects were reported.


CONCLUSIONS
Our results imply a low-dosage, suitable alternative to the common AMPT procedure. The probability of side effects and study withdrawal can be reduced by this procedure.
Boot
Erik
E
Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Meibergdreef 5, 1070 AW Amsterdam, The Netherlands. h.j.boot@amc.uva.nl
Booij
Jan
J
Hasler
Gregor
G
Zinkstok
Janneke R
JR
de Haan
Lieuwe
L
Linszen
Don H
DH
van Amelsvoort
Thérèse A
TA
D000328:Adult; D001549:Benzamides; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004361:Drug Tolerance; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D011388:Prolactin / Q000097:blood; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D009435:Synaptic Transmission; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D019805:alpha-Methyltyrosine / Q000008:administration & dosage / Q000009:adverse effects
D001549:Benzamides; D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D019805:alpha-Methyltyrosine; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D011388:Prolactin; D004298:Dopamine