Comparison between phenylpropanolamine and structurally related compounds on gastric transit in the rat.
Our laboratory previously reported several pharmacological differences between phenylpropanolamine [PPA; (+/-)-norephedrine] and its structurally related compounds in regard to their activity on cardiovascular and appetite-suppressant parameters. The present study investigates the pharmacological differences between PPA, [1R,2R]-(-)-norephedrine [(-)-NOR], [1S,2S]-(+)-norephedrine [(+)-NOR], [1R,2S]-(-)-ephedrine [(-)-EPH], [1S,2R]-(+)-ephedrine [(+)-EPH], [1R,2S]-(-)-norpseudoephedrine [(-)-NORP], [1S,2R]-(+)-norpseudoephedrine [(+)-NORP], [1R,2R]-(-)-pseudoephedrine [(-)-PSE], and [1S,2S]-(+)-pseudoephedrine [(+)-PSE], as determined by their ability to inhibit gastric transit in the rat. (-)-Norephedrine was approximately three times more potent in inhibiting gastric transit than (+)-NOR (p < 0.01). As anticipated, the racemic mixture, PPA, demonstrated an ED50 (25.1 mg/kg) of approximately the mean of the ED50s from the component enantiomers (14.7 and 47.0 mg/kg, respectively). Similarly, administration of 20 mg/kg of either (-)-EPH, (+)-EPH, (-)-PSE, or (+)-PSE significantly decreased gastric transit by 26% (p < 0.001), 12% (p < 0.01), 10% (p < 0.01), and 11% (p < 0.01), respectively. Administration of (-)-NORP and (+)-NORP were without effect. These data confirm and extend previous findings demonstrating pharmacological differences between PPA and its structurally related compounds.
Hull
K M
KM
Department of Pharmacology, Massachusetts College of Pharmacy and Allied Health Sciences, Boston 02115.
Zanzillari
R
R
Maher
T J
TJ
D000818:Animals; D003864:Depression, Chemical; D005772:Gastrointestinal Transit / Q000187:drug effects*; D008297:Male; D010665:Phenylpropanolamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D010665:Phenylpropanolamine