Modification of the duration of action and pharmacodynamics of arecoline by tetraisopropylpyrophosphoramide.
Tetraisopropylpyrophosphoramide (ISO-OMPA) pretreatment in the mouse was examined for its ability to prolong the time course of arecoline (ARE) concentration using brain ARE concentration as an index. Brain ARE levels were also correlated with acetylcholine (ACh) and choline concentrations. Pretreatment with 40 mg kg-1 ISO-OMPA increased ARE brain concentrations from 3 nmoles g-1 to 76 nmoles g-1 15 min after i.p. administration of 25 mg kg-1 ARE. ARE (25 mg kg-1) alone significantly increased brain ACh and choline levels. In time course studies, administration of ARE (15 mg kg-1) produced a peak brain level of 7.9 nmoles g-1 at 3 min. ISO-OMPA pretreatment increased the peak level of ARE to 46.5 nmoles g-1 and the peak time to 7-15 min. The time of maximum brain elevation of ACh and choline produced by ARE alone lagged slightly behind the peak level time observed for ARE. ARE alone produced a maximal increase in ACh and choline levels to 34.1 and 57.1 nmoles g-1, respectively. In the presence of ISO-OMPA, ARE further increased ACh and choline levels to 48.2 and 103 nmoles g-1, respectively. After i.p. administration the highest concentration of ARE was found in the cortex, followed by the subcortex, and cerebellum. A significant elevation of ACh was observed in the cortex.
Patterson
T A
TA
College of Pharmacy, University of South Carolina, Columbia 29208.
Kosh
J W
JW
D000109:Acetylcholine / Q000032:analysis; D000818:Animals; D001115:Arecoline / Q000493:pharmacokinetics*; D001923:Brain Chemistry; D002794:Choline / Q000032:analysis; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013770:Tetraisopropylpyrophosphamide / Q000008:administration & dosage* / Q000494:pharmacology
D001115:Arecoline; D013770:Tetraisopropylpyrophosphamide; D002794:Choline; D000109:Acetylcholine