Peripherally selective piperidine opioid antagonists

A trans 3,4-isomer of a compound of the formula I ##STR14## wherein:

• R.sup.1 is H or (C.sub.1 -C.sub.5) alkyl;
• R.sup.2 is H, (C.sub.1 -C.sub.5) alkyl, or (C.sub.2 -C.sub.6) alkenyl;
• R.sup.3 is H, (C.sub.1 -C.sub.10) alkyl, (C.sub.3 -C.sub.8) cycloalkyl, (C.sub.3 -C.sub.10) alkenyl, (C.sub.3 -C.sub.8) cycloalkyl-(C.sub.1 -C.sub.3) alkyl, phenyl, (C.sub.5 -C.sub.8) cycloalkenyl, (C.sub.5 -C.sub.8) cycloalkenyl(C.sub.1 -C.sub.3)alkyl, or phenyl-(C.sub.1 -C.sub.3) alkyl;
• R.sup.4 is H, (C.sub.3 -C.sub.8) cycloalkyl, (C.sub.1 -C.sub.10) alkyl, (C.sub.3 -C.sub.10) alkenyl), (C.sub.3 -C.sub.8) cycloalkyl-(C.sub.1 -C.sub.3)alkyl, phenyl or phenyl- (C.sub.1 -C.sub.3) alkyl;
• R.sup.5 is H, (C.sub.1 -C.sub.10))alkyl (C.sub.1 -C.sub.10)alkanoyl, C(O)CH--[(CH.sub.2).sub.3 NHC(NH)NHNO.sub.2 ]NHC(O)W, C(O)NH(C.sub.1 -C.sub.10)alkyl, [C(O)--(CH.sub.2).sub.m C(O)].sub.q R.sup.6, or [C(O)(CH.sub.2).sub.m NHC(O)].sub.q R.sup.6 ;
• W is (C.sub.1 -C.sub.10)alkyl, O(C.sub.1 -C.sub.10)alkyl, (C.sub.1 -C.sub.4 alkyl)NHC(O)(C.sub.1 -C.sub.6)- alkyl, or (C.sub.1 -C.sub.4 alkyl)C(O)NHB, where B is (C.sub.1 -C.sub.10)- alkyl, phenyl or phenyl-(C.sub.1 -C.sub.3)alkyl;
• R.sup.6 is OR.sup.7, NHR.sup.7, OCH.sub.2 C(O)NR.sup.8 R.sup.9, O(C.sub.1 -C.sub.4 alkyl)OC--(O)R.sup.10, (C.sub.1 -C.sub.10) alkyl, or NHCHR.sup.11 C(O)R.sup.12
• R.sup.7 is H, (C.sub.1 -C.sub.10)alkyl, (C.sub.3 -C.sub.8)cycloalkyl, (C.sub.3 -C.sub.8)cycloalkyl-(C.sub.1 -C.sub.3) alkyl or (CH.sub.2).sub.m C(O)NR.sup.8 R.sup.9 ;
• R.sup.8 is H, or (C.sub.1 -C.sub.10)alkyl;
• R.sup.9 is H, or (C.sub.1 -C.sub.10)alkyl;
• R.sup.10 is (C.sub.1 -C.sub.10)alkyl, or (C.sub.3 -C.sub.8)cycloalkyl;
• R.sup.11 is H, (C.sub.1 -C.sub.10))alkyl, or phenyl-(C.sub.1 -C.sub.3)alkyl;
• R.sup.12 is OR.sup.13 or NR.sup.13 R.sup.14 ;
• R.sup.13 is H or (C.sub.1 -C.sub.10)alkyl;
• R.sup.14 is H or (C.sub.1 -C.sub.10)alkyl;
• n=1-3;
• m=1-3;
• q=1-3;
• or
• a pharmaceutically acceptable salt thereof.