Oxytocin by intranasal and intravenous routes reaches the cerebrospinal fluid in rhesus macaques: determination using a novel oxytocin assay.
Oxytocin by intranasal and intravenous routes reaches the cerebrospinal fluid in rhesus macaques: determination using a novel oxytocin assay.
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DOI：
10.1038/mp.2017.27
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发表时间：
2018-01
影响因子：
11
通讯作者：
Averbeck BB
中科院分区：
文献类型：
--
作者：
Lee MR;Scheidweiler KB;Diao XX;Akhlaghi F;Cummins A;Huestis MA;Leggio L;Averbeck BB
催产素（OT）是一种治疗多种神经精神疾病的潜在药物。由于OT是一种肽，鼻内给药是临床研究中首选的方法。虽然研究表明，在给药后脑脊液（CSF） OT水平升高，但这并不能清楚地证明外周给药的OT正在进入CSF。例如，有人认为外周传递OT可能导致内源性OT的中枢释放。与需要穿透血脑屏障（BBB）的静脉注射途径相比，静脉注射途径是否能使肽更有效地进入脑脊液，这也是未知的。为了解决这些问题，我们开发了一种灵敏而特异的定量质谱分析方法，可以区分标记的（d5-氘化）OT和内源性（d0） OT。我们给6只非人灵长类动物注射催产素（80 IU），并通过静脉注射和生理盐水作为对照。我们在给药前（t=0）和给药后（t=10、20、30、45、60分钟）测量给药OT和内源性OT的血浆和脑脊液浓度。我们证明了脑脊液的d5外显性，外源性OT通过IN和IV给药。外周给药d5-OT不导致脑脊液内源性OT升高。这表明外周给药OT不会导致内源性OT的中枢释放。我们也没有发现与静脉给药相比，静脉给药在获得更高的脑脊液OT浓度方面具有优势。
Oxytocin (OT) is a potential treatment for multiple neuropsychiatric disorders. Since OT is a peptide, delivery by the intranasal (IN) route is the preferred method in clinical studies. Although studies have shown increased cerebrospinal fluid (CSF) OT levels following IN administration, this does not clearly demonstrate that the peripherally administered OT is entering the CSF. For example, it has been suggested that peripheral delivery of OT could lead to central release of endogenous OT. It is also unknown whether the IN route provides for more efficient entry of the peptide into the CSF compared to the IV route which requires blood brain barrier (BBB) penetration. To address these questions, we developed a sensitive and specific quantitative mass spectrometry assay that distinguishes labelled (d5-deuterated) from endogenous (d0) OT. We administered d5-oxytocin (80 IU) to 6 nonhuman primates via IN and IV routes as well as IN saline as a control condition. We measured plasma and CSF concentrations of administered and endogenous OT before (t=0) and after (t=10, 20, 30, 45, 60 minutes) d5-oxytocin dosing. We demonstrate CSF penetrance of d5, exogenous OT delivered by IN and IV administration. Peripheral administration of d5-OT did not lead to increased d0, endogenous OT in the CSF. This suggests that peripheral administration of OT does not lead to central release of endogenous OT. We also did not find that IN administration offered an advantage compared to IV administration with respect to achieving greater CSF concentrations of OT.
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影响因子：
3.7
作者：
Modi, Meera E.;Connor-Stroud, Fawn;Landgraf, Rainer;Young, Larry J.;Parr, Lisa A.
通讯作者：
Parr, Lisa A.
影响因子：
2.4
作者：
Vyas, Tushar K.;Shahiwala, Aliasgar;Misra, Ambikanandan
通讯作者：
Misra, Ambikanandan
DOI：
10.1073/pnas.1509795112
发表时间：
2015-11-10
影响因子：
11.1
作者：
Wei, Don;Lee, DaYeon;Piomelli, Daniele
通讯作者：
Piomelli, Daniele
人类鼻内给药后催产素的脑脊液和血液浓度升高
影响因子：
4.6
作者：
Striepens N;Kendrick KM;Hanking V;Landgraf R;Wüllner U;Maier W;Hurlemann R
通讯作者：
Hurlemann R
影响因子：
3.3
作者：
Szeto A;McCabe PM;Nation DA;Tabak BA;Rossetti MA;McCullough ME;Schneiderman N;Mendez AJ
通讯作者：
Mendez AJ