Amphetamine enantiomers inhibit homomeric α7 nicotinic receptor through a competitive mechanism and within the intoxication levels in humans.
Amphetamine enantiomers inhibit homomeric α7 nicotinic receptor through a competitive mechanism and within the intoxication levels in humans.
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DOI：
10.1016/j.neuropharm.2018.10.032
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发表时间：
2019-01
影响因子：
4.7
通讯作者：
Lizardi-Ortiz JE
中科院分区：
文献类型：
--
作者：
Garton DR;Ross SG;Maldonado-Hernández R;Quick M;Lasalde-Dominicci JA;Lizardi-Ortiz JE
Amphetamine-type stimulants (ATS) are the second most consumed illicit drug worldwide and lack good treatments for associated substance use disorders, lagging behind other addictive drugs. For this reason, a deeper understanding of the pharmacodynamics of ATS is required. The present study seeks to determine amphetamine (AMPH) enantiomers’ effects on the homomeric α 7 nicotinic acetylcholine receptor (α7 nAChR). Here we have shown that AMPH enantiomers bind to the α 7 nAChR and competitively inhibit acetylcholine responses. Our in silico docking analysis suggests that AMPH binds close to the β7 strand of the B-loop of a chimera comprising of the human α7 nAChR and the acetylcholine binding protein from Lymnaea stagnalis. This may inhibit the required movement of the C-loop for channel opening, due to steric hindrance, providing a structural mechanism for its antagonist effect. Finally, we have shown that, in α7 nAChR full knockout mice, the behavioral response to D-AMPH is attenuated, providing direct evidence for the role of α 7 nAChRs on the physiological response to D-AMPH. Importantly, D-AMPH exerts these effects at concentrations predicted to be pharmacologically relevant for chronic methamphetamine users and during binges. In conclusion, our data present new findings that implicate the α 7 nAChR on the pharmacodynamics of ATS, which may be important for behavioral responses to these drugs, indicating a potential role for α 7 nAChRs in ATS substance-use disorders.
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DOI：
10.1111/ejn.12114
发表时间：
2013-03
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Baker LK;Mao D;Chi H;Govind AP;Vallejo YF;Iacoviello M;Herrera S;Cortright JJ;Green WN;McGehee DS;Vezina P
通讯作者：
Vezina P
DOI：
10.1073/pnas.0807635105
发表时间：
2008-10-14
影响因子：
11.1
作者：
Avale, Maria Elena;Faure, Philippe;Maskos, Uwe
通讯作者：
Maskos, Uwe
影响因子：
3.8
作者：
Brensilver, Matthew;Heinzerling, Keith G.;Shoptaw, Steven J.
通讯作者：
Shoptaw, Steven J.
影响因子：
1.6
作者：
Camarasa, Jorge;Garcia Rates, Sara;Escubedo, Elena
通讯作者：
Escubedo, Elena
影响因子：
7.3
作者：
de Kloe, Gerdien E.;Retra, Kim;de Esch, Iwan J. P.
通讯作者：
de Esch, Iwan J. P.