Why does alcohol reduce shyness?
It has to do with the excitatory affect alcohol has on almost all neurotransmitters and their receptors, including serotonin, dopamine, and GABA.

Very, very broadly: 
Serotonin: Generally makes one seek a human connection.
Dopamine: Motivation to do things that are stimulating, like conversation.
Gaba: Surpresses anxiety.

GHB will do this even more - but it may do it to way too much of an extent.  (Mostly Gaba, but increases tyrosine hydroxylase as well which = more dopamine.)
MDMA obviously (it causes your serotonin receptors to instead of soaking up the neurotransmitter pump them out).
Amphetamines to an extent.  (Similar to the last two)