PMID- 26954347
OWN - NLM
STAT- MEDLINE
DCOM- 20170406
LR  - 20170406
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Linking)
VI  - 29
IP  - 5
DP  - 2016 May 16
TI  - Impact of Functional Group Modifications on Designer Phenethylamine Induced 
      Hyperthermia.
PG  - 871-8
LID - 10.1021/acs.chemrestox.6b00030 [doi]
AB  - The popularity of designer phenethylamines such as synthetic cathinones ("bath 
      salts") has led to increased reports of life-threatening hyperthermia. The 
      diversity of chemical modifications has resulted in the toxicological profile of 
      most synthetic cathinones being mostly uncharacterized. Here, we investigated the 
      thermogenic effects of six recently identified designer phenethylamines 
      (4-methylmethamphetamine, methylone, mephedrone, butylone, pentylone, and MDPV) 
      and compared these effects to the established thermogenic agent 
      3,4-methylenedioxymethamphetamine (MDMA). Specifically, we determined the impact 
      of a beta-ketone, alpha-alkyl, or pyrrolidine functional group on core-body temperature 
      changes. Sprague-Dawley rats (n = 5-6) were administered a dose (30 mg/kg, sc) of 
      a designer phenethylamine or MDMA, and core body temperature measurements were 
      recorded at 30 min intervals for 150 min post treatment. MDMA elicited the 
      greatest maximum temperature change (DeltaTmax), and this effect was significantly 
      greater than that of its beta-ketone analogue, methylone. Temperature-area under the 
      curves (TAUCs) and DeltaTmax were also significantly different between 
      4-methylmethamphetamine (4-MMA) and its beta-ketone analogue mephedrone. Lengthening 
      the alpha-alkyl chain of methylone to produce butylone and pentylone significantly 
      attenuated the thermogenic response on both TAUCs and DeltaTmax compared to those of 
      methylone; however, butylone and pentylone were not different from each other. 
      Pyrrolidine substitution on the N-terminus of pentylone produces 
      3,4-methylenedioxypyrovalerone (MDPV), which did not significantly alter core 
      body temperature. Thermogenic comparisons of MDMA vs methylone and 4-MMA vs 
      mephedrone indicate that oxidation at the benzylic position significantly 
      attenuates the hyperthermic response. Furthermore, either extending the alpha-alkyl 
      chain to ethyl and propyl (butylone and pentylone, respectively) or extending the 
      alpha-alkyl chain and adding a pyrrolidine on the N-terminus (MDPV) significantly 
      blunted the thermogenic effects of methylone. Overall, the present study provides 
      the first structure-activity relationship in vivo toxicological analysis of 
      designer phenethylamines.
FAU - Grecco, Gregory G
AU  - Grecco GG
AD  - The Ohio Attorney General's Center for the Future of Forensic Science, Bowling 
      Green State University , Bowling Green, Ohio 43403, United States.
FAU - Sprague, Jon E
AU  - Sprague JE
AD  - The Ohio Attorney General's Center for the Future of Forensic Science, Bowling 
      Green State University , Bowling Green, Ohio 43403, United States.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160316
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Ketones)
RN  - 0 (Phenethylamines)
RN  - 0 (Sympathomimetics)
RN  - 327C7L2BXQ (phenethylamine)
SB  - IM
MH  - Animals
MH  - Fever/*chemically induced
MH  - Ketones/chemistry
MH  - Male
MH  - Phenethylamines/*chemistry
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sympathomimetics/adverse effects
EDAT- 2016/03/10 06:00
MHDA- 2017/04/07 06:00
CRDT- 2016/03/09 06:00
PHST- 2016/03/09 06:00 [entrez]
PHST- 2016/03/10 06:00 [pubmed]
PHST- 2017/04/07 06:00 [medline]
AID - 10.1021/acs.chemrestox.6b00030 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2016 May 16;29(5):871-8. doi: 10.1021/acs.chemrestox.6b00030. 
      Epub 2016 Mar 16.