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| Content Provider | PubMed Central |
|---|---|
| Author | Semba, J. Curzon, G. Patsalos, P. N. |
| Abstract | 1. The kinetics and metabolism of milacemide have been studied in an animal model which allows the simultaneous investigation of the temporal inter-relationships of drugs and metabolites in blood (pharmacokinetics) and cerebrospinal fluid (CSF, neuropharmacokinetics) in individual freely moving rats. 2. Milacemide dose-dependently increased CSF glycine and glycinamide (intermediary metabolite) concentrations. This confirms that milacemide is a CNS glycine prodrug. 3. Pretreatment with L-deprenyl (2 mg kg-1), a specific inhibitor of monoamine oxidase type B (MAO-B), almost completely prevented the formation of glycinamide and increased milacemide accumulation in CSF. Tmax and t1/2 were significantly increased and Cmax and AUC values were decreased for glycinamide compared to controls. Pretreatment with clorgyline (5 mg kg-1), a specific inhibitor of MAO-type A, only moderately decreased glycinamide Cmax and AUC values. 4. After milacemide administration (100, 200 and 400 mg kg-1, i.p.) serum and CSF milacemide concentrations rose linearly and dose-dependently. Serum glycinamide concentrations exhibited small dose-dependent rises but these were not linearly related. In contrast, CSF glycinamide concentrations rose linearly and dose-dependently with Cmax values 2.5, 3.2 and 4.1 times greater than the corresponding values for serum glycinamide after giving 100, 200 and 400 mg kg-1 respectively of milacemide. 5. Serum glycine concentrations were unaffected but CSF concentrations increased dose-dependently and these were significant at the higher milacemide doses (200 and 400 mg kg-1). Animals given 400 mg kg-1 milacemide had glycine values which were still significantly elevated 7 h later.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Starting Page | 1117 |
| File Format | |
| ISSN | 00071188 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 108 |
| Language | English |
| Publisher Date | 1993-04-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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