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P. to mice as suspensions the pro-drugs d i s solved s l o w l y , g r a d u a l l y r e l e a s i n g XC to the c i r c u l a t i o n where the d e r i v a t i v e s were enzymatically cleaved to LXXXIX a l l o w i n g i t to exert i t s pharmacological act i v i t y . Gray et a l . (258) demonstrated a q u a l i t a t i v e c o r r e l a t i o n between a c t i v i t y of the XC d e r i v a t i v e s and decreasing aqueous s o l u b i l i t y suggesting that the slow d i s s o l u t i o n of the suspension of the 5 - e s t e r s was important.

The q u a n t i t a t i v e conversion of XXXIX to XXXVIII i n mouse b r a i n homogenates was a l s o observed. ; ACS Symposium Series; American Chemical Society: Washington, DC, 1975. 1. STELLA Overview and Definition 29 compound by the a d m i n i s t r a t i o n of i t s t e r t i a r y ω-haloalkylamine precursor. The study of the e l i m i n a t i o n of quaternary compounds from the CNS has been l i m i t e d by absorption, i . e . , the study of e l i m i n a t i o n i s d i f f i ­ c u l t i f i t has never been e s t a b l i s h e d that the quater­ nary compound was e f f e c t i v e l y absorbed i n the f i r s t place.

O i l i n j e c t i o n was c l o s e l y r e l a t e d to the o i l / w a t e r d i s t r i b u t i o n c o e f f i c i e n t of the d e r i v a t i v e s . The o i l used by James ejb a l . ( 2 6 4 ) was e t h y l o l e a t e . I t was i n t e r e s t i n g to note that the homologous s e r i e s of f o r myl through v a l e r y l esters of testosterone had approximately equal s o l u b i l i t y i n the e t h y l oleate showing that the d i s t r i b u t i o n c o e f f i c i e n t was l a r g e l y determined by the decrease i n water s o l u b i l i t y .

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