eth ox y - ester ▁functional ▁rep lac ements ▁▁ 2 0 1 b ▁& ▁ 2 0 1 c ▁show ▁significant ▁increased ▁pot ency ▁over ▁c oca ine ; ▁whereas ▁ 2 0 1 a , ▁ 2 0 1 d ▁& ▁ 2 0 1 e ▁are ▁consider ably ▁less ▁so . ▁This ▁inf ers ▁the ▁hydro gen ▁bond ▁accept or ▁at ▁the ▁ 2 β ▁position ▁to ▁not ▁necessarily ▁be ▁of ▁exclusive ▁import ▁in ▁creation ▁of ▁higher ▁binding ▁analog ues ▁of ▁c oca ine . ▁ ▁N - mod ifications ▁▁▁▁▁ ɑ IC 5 0 ▁( n M ) ▁for ▁disp lacement ▁of ▁[ 3 H ] WIN ▁ 3 5 4 2 8 ▁ ▁Br id ged ▁( N - const rained / t ether ed ) ▁trop ane - f used ▁c oca ine ▁analog ues ▁▁ 8 ▁to ▁ 2 ▁position ▁trop ane ▁bridge ▁ ▁Back - brid ged ▁c oca ine ▁analog ues ▁are ▁considered ▁more ▁a kin ▁to ▁un t ether ed ▁c oca ine ▁anal ogs ▁& ▁ph eny lt rop ane ▁derivatives ▁( where ▁the ▁nit ro gen ▁l one ▁pair ▁is ▁not ▁fixed ▁or ▁const rained ) ▁and ▁better ▁m im ics ▁their ▁aff in ities . ▁This ▁is ▁due ▁to ▁when ▁the ▁e ighth ▁carbon ▁trop ane ▁position ▁is ▁freely ▁rot atable ▁and ▁un bound ▁it ▁prefer ably ▁occup ies ▁the ▁ax ial ▁position ▁as ▁defining ▁its ▁least ▁energy ▁& ▁most ▁unh inder ed ▁state . ▁In ▁front - brid ged