The quaternary salt of morphine contains a permanent positive charge. If thecompound is administered
in vivo,
it has to cross the blood brain barrier in order toreach the analgesic receptors in the brain. However, the blood brain barrier ishydrophobic, and since the compound has a permanent positive charge, it cannotcross. Thus, the observed inactivity
in vivo
is due to the inability of the compound toreach the receptors in the brain.
In vitro
tests are carried out on isolated receptors or cells and so there is no blood brain barrier to cross