title: Endocrine and neurochemical effects of 3,4-methylenedioxymethamphetamine and its stereoisomers in rhesus monkeys.
abstract: 3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative that elicits complex biological effects in humans. One plausible mechanism for this phenomenon is that racemic MDMA is composed of two stereoisomers that exhibit qualitatively different pharmacological effects. In support of this, studies have shown that R(-)-MDMA tends to have hallucinogen-like effects, whereas S(+)-MDMA tends to have psychomotor stimulant-like effects. However, relatively little is known about whether these stereoisomers engender different endocrine and neurochemical effects. In the present study, the endocrine and neurochemical effects of each stereoisomer and the racemate were assessed in four rhesus monkeys after intravenous delivery at doses (1-3 mg/kg) that approximated voluntary self-administration by rhesus monkeys and human recreational users. Specifically, fluorescence-based enzyme-linked immunosorbent assay was used to assess plasma prolactin concentrations, and in vivo microdialysis was used to assess extracellular dopamine and serotonin concentrations in the dorsal striatum. R(-)-MDMA, but not S(+)-MDMA, significantly increased plasma prolactin levels and the effects of S,R(+/-)-MDMA were intermediate to each of its component stereoisomers. Although S(+)-MDMA did not alter prolactin levels, it did significantly increase extracellular serotonin concentrations. In addition, S(+)-MDMA, but not R(-)-MDMA, significantly increased dopamine concentrations. Furthermore, as in the prolactin experiment, the effects of the racemate were intermediate to each of the stereoisomers. These studies demonstrate the stereoisomers of MDMA engender qualitatively different endocrine and neurochemical effects, strengthening the inference that differences in these stereoisomers might be the mechanism producing the complex biological effects of the racemic mixture of MDMA in humans.
authors.affiliation: Division of Neuroscience, Yerkes National Primate Research Center, Atlanta, Georgia 30322, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Murnane
authors.forename: W E
authors.initials: WE
authors.lastname: Fantegrossi
authors.forename: J R
authors.initials: JR
authors.lastname: Godfrey
authors.forename: M L
authors.initials: ML
authors.lastname: Banks
authors.forename: L L
authors.initials: LL
authors.lastname: Howell
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000697:Central Nervous System Stimulants / Q000737:chemistry / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006213:Hallucinogens / Q000737:chemistry / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008253:Macaca mulatta; D017551:Microdialysis; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000737:chemistry / Q000494:pharmacology*; D011388:Prolactin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000697:Central Nervous System Stimulants; D006213:Hallucinogens; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D011388:Prolactin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine; D006719:Homovanillic Acid
references.citation: Exp Clin Psychopharmacol. 2008 Feb;16(1):1-12
references.pmid: 18266547
references.citation: Neuropsychopharmacology. 2004 Jul;29(7):1270-81
references.pmid: 15039771
references.citation: J Pharm Sci. 1986 Nov;75(11):1019-27
references.pmid: 3820095
references.citation: Psychopharmacology (Berl). 1997 Mar;130(1):2-13
references.pmid: 9089844
references.citation: Psychopharmacology (Berl). 2008 Jan;196(1):63-70
references.pmid: 17899019
references.citation: Psychopharmacology (Berl). 2007 Jan;189(4):471-82
references.pmid: 16555062
references.citation: J Pharmacol Exp Ther. 1994 Oct;271(1):143-8
references.pmid: 7965707
references.citation: Pharmacol Biochem Behav. 1988 Mar;29(3):443-9
references.pmid: 2896360
references.citation: Mol Pharmacol. 2003 Jun;63(6):1223-9
references.pmid: 12761331
references.citation: Psychopharmacology (Berl). 2003 Mar;166(3):202-11
references.pmid: 12563544
references.citation: Psychopharmacology (Berl). 2007 Jan;189(4):483-8
references.pmid: 17063335
references.citation: J Psychoactive Drugs. 1986 Oct-Dec;18(4):291-304
references.pmid: 2880943
references.citation: Behav Pharmacol. 1995 Apr;6(3):263-275
references.pmid: 11224335
references.citation: Psychopharmacology (Berl). 2002 Jun;161(4):356-64
references.pmid: 12073162
references.citation: Brain Res. 2009 Feb 3;1252:87-93
references.pmid: 19059385
references.citation: Neuroscience. 2008 Mar 27;152(3):773-84
references.pmid: 18313226
references.citation: Synapse. 2002 Jan;43(1):78-85
references.pmid: 11746736
references.citation: J Endocrinol. 1989 Dec;123(3):393-402
references.pmid: 2607250
references.citation: Psychopharmacology (Berl). 2009 Aug;205(3):467-74
references.pmid: 19430765
references.citation: J Pharmacol Exp Ther. 1997 Dec;283(3):1305-22
references.pmid: 9400006
references.citation: Bioorg Med Chem Lett. 2004 May 3;14(9):2367-70
references.pmid: 15081042
references.citation: Drug Alcohol Depend. 2006 May 20;82(3):276-81
references.pmid: 16289931
references.citation: Psychopharmacol Ser. 1988;4:161-75
references.pmid: 3293041
references.citation: Pharmacol Biochem Behav. 2007 Jan;86(1):45-54
references.pmid: 17258302
references.citation: Eur J Pharmacol. 1994 Nov 3;264(3):325-30
references.pmid: 7698172
references.citation: Brain Res. 2004 Aug 6;1016(2):240-6
references.pmid: 15246860
references.citation: Addiction. 2002 Dec;97(12):1531-6
references.pmid: 12472637
references.citation: Neuropsychopharmacology. 2004 May;29(5):833-46
references.pmid: 14997175
references.citation: Psychiatry Res. 1995 Sep 29;58(2):89-98
references.pmid: 8570772
references.citation: NIDA Res Monogr. 1978;(22):8-15
references.pmid: 101890
references.citation: Synapse. 2002 Apr;44(1):51-7
references.pmid: 11842446
references.citation: J Psychoactive Drugs. 1986 Oct-Dec;18(4):305-13
references.pmid: 2880944
references.citation: J Pharmacol Exp Ther. 2009 Nov;331(2):717-23
references.pmid: 19684254
references.citation: Psychopharmacology (Berl). 2007 Jan;189(4):407-24
references.pmid: 16541247
references.citation: Drug Alcohol Depend. 2006 Jan 4;81(1):27-36
references.pmid: 15975736
references.citation: J Pharmacol Exp Ther. 2002 Jun;301(3):1097-102
references.pmid: 12023542
references.citation: Neurosci Lett. 1994 Aug 15;177(1-2):111-5
references.pmid: 7824160
references.citation: Psychoneuroendocrinology. 2004 Feb;29(2):185-200
references.pmid: 14604600
references.citation: Psychoneuroendocrinology. 2005 Apr;30(3):273-83
references.pmid: 15511601
references.citation: Synapse. 2005 Dec 15;58(4):220-8
references.pmid: 16206183
references.citation: Neuropharmacology. 1990 Mar;29(3):269-75
references.pmid: 1691459
references.citation: Drug Alcohol Depend. 2003 Oct 24;72(1):33-44
references.pmid: 14563541
references.citation: J Pharmacol Exp Ther. 2008 Oct;327(1):38-44
references.pmid: 18591215
references.citation: Psychopharmacology (Berl). 2000 Feb;148(3):299-306
references.pmid: 10755743
references.citation: Psychopharmacology (Berl). 2002 Aug;162(4):396-405
references.pmid: 12172693
references.citation: Drugs. 1983 Apr;25(4):399-432
references.pmid: 6133737
references.citation: Life Sci. 1984 Apr 2;34(14):1325-31
references.pmid: 6708733
references.citation: J Neurochem. 2007 Jul;102(1):121-32
references.pmid: 17564678
references.citation: Pharmacol Rev. 2003 Sep;55(3):463-508
references.pmid: 12869661