Effect of hydroxypropyl-beta-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 (Kb) and rate constant (Kc) 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.
Walker
R B
RB
Department of Chemistry and Physics, University of Arkansas at Pine Bluff 71611, USA. walker_r@vx4500.uapb.edu
Dholakia
V N
VN
Brasfield
K L
KL
Bakhtiar
R
R
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D018663:Adrenergic Agents / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003505:Cyclodextrins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004809:Ephedrine / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D013058:Mass Spectrometry; D010080:Oxazoles / Q000378:metabolism / Q000494:pharmacology*; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D047392:beta-Cyclodextrins
D018663:Adrenergic Agents; D003505:Cyclodextrins; D010080:Oxazoles; D011355:Prodrugs; D047392:beta-Cyclodextrins; C064210:oxazolidine; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D004809:Ephedrine