▁ten ▁times ▁stronger ▁than ▁c oca ine ▁as ▁a ▁dop am ine ▁re upt ake ▁p ump ▁lig and , ▁and ▁twenty ▁four ▁times ▁stronger ▁as ▁a ▁local ▁an est h etic ▁( vol t age - dependent ▁Na + ▁channel ▁block er ), ▁whereas ▁the ▁C 1 ▁m eth yl ▁analog ▁is ▁ 2 . 3 ▁times ▁less ▁pot ent ▁as ▁a ▁local ▁an est h etic . ▁▁ 2 β - subst itution s ▁( including ▁trans ester ification ▁met abol ite ▁substitution ▁c oca eth yl ene ) ▁ ▁The ▁consideration ▁that ▁large , ▁bul ky ▁C 2 ▁subst itu ents ▁would ▁alter ▁the ▁trop ane ▁by ▁dist ort ing ▁the ▁pi per id ine ▁ring ▁part ▁of ▁its ▁ske leton ▁sufficiently ▁enough ▁to ▁imp air ▁its ▁functionality , ▁or ▁that ▁in ▁said ▁event ▁such ▁would ▁ham per ▁binding , ▁in ▁particular ▁at ▁the ▁ 8 - aza ▁end ▁to ▁ease ▁ster ic ▁stra in ▁going ▁toward ▁its ▁place ▁from ▁the ▁ 2 - position , ▁appear ▁to ▁in ▁many ▁cases ▁be ▁unf ounded . ▁( examples ▁shown ▁in ▁table ▁of ▁images ▁below ) ▁ ▁Comp ound ▁ 1 9 7 b ▁displayed ▁a ▁ 1 , 1 3 1 - fold ▁increased ▁select ivity ▁in ▁aff inity ▁over ▁the ▁ser ot on in ▁trans porter , ▁with ▁only ▁slight ▁redu ctions ▁in ▁pot ency ▁for ▁the ▁dop am ine ▁& ▁n ore pine phr ine ▁trans por ters . ▁Where as ▁ 1 9 7 c ▁had ▁a ▁