کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2493958 | 1115537 | 2010 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
In vitro and in vivo characterization of a novel negative allosteric modulator of neuronal nAChRs
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: In vitro and in vivo characterization of a novel negative allosteric modulator of neuronal nAChRs In vitro and in vivo characterization of a novel negative allosteric modulator of neuronal nAChRs](/preview/png/2493958.png)
چکیده انگلیسی
In this study, we compared the in vitro and in vivo neuronal nicotinic acetylcholine receptor (nAChR) properties of 1,2,3,3a,4,8b-hexahydro-2-benzyl-6-N,N-dimethylamino-1-methylindeno[1,2,-b]pyrrole (HDMP, 4) to that of negative allosteric modulator (NAM), PCP. Patch-clamp experiments showed that HDMP exhibited an inhibitory functional activity at α7 nAChRs with an IC50 of 0.07 μM, and was 357- and 414-fold less potent at α4β2 and α3β4 nAChRs, with IC50s of 25.1 and 29.0 μM, respectively. Control patch-clamp experiments showed that PCP inhibited α7, α4β2 and α3β4 nAChRs with IC50s of to 1.3, 29.0 and 6.4 μM, respectively. Further, HDMP did not exhibit any appreciable binding affinity to either α7 or α4β2 nAChRs, suggesting its action via a non-competitive mechanism at these neuronal nAChR subtypes. The in vivo study showed that HDMP was a potent antagonist of nicotine-induced analgesia in the tail-flick (AD50 = 0.008 mg/kg), but not in the hot-plate test. All together, our in vitro and in vivo data suggest that HDMP is a novel NAM of neuronal nAChRs with potent inhibitory activity at α7 nAChR subtype at concentrations â¤1 μM that are not effective for α4β2 and α3β4 nAChRs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 59, Issue 6, November 2010, Pages 511-517
Journal: Neuropharmacology - Volume 59, Issue 6, November 2010, Pages 511-517
نویسندگان
Galya R. Abdrakhmanova, Bruce E. Blough, Carey Nesloney, Hernán A. Navarro, M. Imad Damaj, F. Ivy Carroll,