NK3 receptor Antagonists
These are found exclusively in brain and spinal cord but their location
is quite restricted and this also possess challenges in development of
NK3 antagonists which are limited comparitivley.85,86Osanetant was the first non-peptide NK3 antagonist described; it was
derived from the known NK2 antagonist saredutant. Osanetant was compared
with three other potential antipsychotics such as the 5-HT2a/5-HT2c
receptor antagonist SR-46349B, the cannabinoid CB1 receptor antagonist
rimonabant and the neurotensin receptor antagonist SR-48692, as well as
with the classical antipsychotic haloperidol and with placebo. There was
no significant difference between the efficacy of Osanetant and
haloperidol in that study.87 Talnetant in a
placebo-controlled trial showed a reduction in clinical symptoms not
better than risperidone however the study showed a good tolerability as
compared to risperidone. 88 But this drug has been
abandoned by the researchers for undisclosed reasons. With all these
inconclusive and a bit contradictory evidences long-term trials of
further improved NK3 antagonists may confirm the positive results
obtained so far with regard to efficacy and tolerability.