Abstract
Recent studies have shown that β2-Adrenoreceptor is a regulator of the a-synuclein gene driving risk of Parkinson’s disease. The β2-AR agonist (R)-salbutamol, eutomer of rac-salbutamol, may hold therapeutic potential for Parkinson’s disease (PD) following nasal administration. In this study, we use desorption electrospray ionization mass spectrometry (DESI-MS) to analyze spatial distribution of (R)-salbutamol in rat brain following nasal and intravenous administration. Here, we report that (R)-salbutamol efficiently deliver to the brain and had more drug dosage exposure in rat’s brain through nasal route administration than that of intravenous route administration. In conclusion, administering (R)-salbutamol through nasal route of administration may hold advantages in improving spatial distribution and increased exposure of drug in brain.
Highlights
Salbutamol is a short-acting β2-AR agonist and it is used for respiratory diseases [1]
Recent studies have demonstrated that use of salbutamol is associated with a decreased Parkinson’s disease (PD) risk (β2-Adrenoreceptor is a regulator of the a-synuclein gene driving risk of Parkinson’s disease) [2,3]
(R)-salbutamol can activate adenylate cyclase and increase the content of cAMP in cells, and increased cAMP will inhibit the release of inflammatory factors produced by mast cells and eosinophils [9]. (S)-salbutamol, will inhibit adenylate cyclase, cause the decrease of cAMP content, and have the opposite effect with (R)-salbutamol [10]
Summary
Salbutamol is a short-acting β2-AR agonist and it is used for respiratory diseases (structure shown in Figure 1) [1]. Binding of (R)-salbutamol and S-salbutamol with β2-receptor has opposite effects on calcium concentration, bronchoconstriction, airway responsiveness and eosinophils [5,6,7,8]. (R)-salbutamol can activate adenylate cyclase and increase the content of cAMP in cells, and increased cAMP will inhibit the release of inflammatory factors produced by mast cells and eosinophils [9]. (S)-salbutamol, will inhibit adenylate cyclase, cause the decrease of cAMP content, and have the opposite effect with (R)-salbutamol [10]. The anatomical structure of the nasal cavity is cloIsnetlyrarnealsaatel dadtmo itnhiestbraratiionn[1is4a]. M(RS)-.salbutamol in rat brain through nasal and intravenous administration using DESI-MS.
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