More Than Just A Love Affair: Oxytocin Receptor Agonists for the Treatment of Social Dysfunction

Abstract

Mental health disorders such as depression and anxiety affect over 1 billion

individuals worldwide and are now the leading cause of disability globally. Declining

mental health can be generally characterised by the existence of abnormal thoughts

and behaviours which hinder regular routines and result in the debilitating cycle of

social withdrawal and isolation. The high incidence of these central nervous system

ailments worldwide emphasises the current lack of effective prevention and the

limitations of treatment. The social dysfunction caused by mental health disorders is

often treated with antidepressants, a class of medication that has become associated

with undesirable side effects which highlights the necessity for improved therapeutics.

Oxytocin, commonly known as the ‘love hormone’, is a large CNS-active

neuropeptide that has demonstrated pro-social behaviour in mammals. Whilst

oxytocin is highly potent at its native receptor, its therapeutic use is greatly limited by

poor selectivity, unsatisfactory drug-like properties (particularly blood-brain barrier

permeability) and rapid metabolism. Consequently, research into small molecules that

selectively activate the oxytocin receptor has started to attract more attention.

The research contained within this thesis focuses on the design, synthesis, and

in vitro evaluation of small molecule oxytocin receptor agonists.