Effect of hydroxypropyl-β-cyclodextrin on the central stimulant activity of (-)-ephedrine and an oxazolidine prodrug in rats

1. Hydroxypropyl beta-cyclodextrin (HP-beta-CD) increases the stability of the oxazolidine prodrug toward hydrolysis. 2. The binding constant (K(b)) and rate constant (K(c)) for the hydrolysis of the prodrug-HP-beta-CD complex were calculated from the kinetic data. 3. Ion spray mass spectra confirmed prodrug-HP-beta-CD complexation. 4. Mass spectral and kinetic data indicated 1:1 stoichiometry for the complex. 5. A significant elevation of locomotor activity in rats was observed when either (-)-ephedrine or the prodrug was administered by either the intraperitoneal or the oral route. 6. Addition of HP-beta-CD potentiated the central nervous system effect of both (-)-ephedrine and the prodrug when administered intraperitoneally. However, when the drugs were administered orally, HP-beta-CD caused a decrease in activity. (C) 1998 Elsevier Science Inc.