Newman-Tancredi A,
Neuropsychiatry, April 2011, Vol. 1, No. 2, Pages 149-164.

Serotonin or 5-hydroxytryptamine 5-HT1A receptors are widely expressed in the brain and have extensive influence in the control of mood, cognition, movement and pain. In order to achieve optimal therapeutic benefit from targeting these receptors, ‘biased agonists’ (also known as ‘functionally selective agonists’) are desirable in order to preferentially activate receptor subpopulations in brain regions that mediate therapeutic activity, whilst avoiding those that control other effects. For example, clinical studies indicate that antidepressant activity is favored when 5-HT1A autoreceptor activation is minimized and postsynaptic 5-HT1A receptor activation is reinforced. F15599 is a novel biased agonist that exhibits a distinctive signal transduction ‘fingerprint’ in vitro and preferential postsynaptic activation of cortical 5-HT1A receptors in vivo. This profile confers on F15599 a superior activity in animal models of depression and cognition, with a wide therapeutic margin relative to side effects. The use of biased agonists at 5-HT1A receptors constitutes an attractive strategy to manage CNS disorders arising from dysfunctional serotonergic neurotransmission.

Promising pipeline

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Therapeutic focus

Neurolixis is developing clinical phase drugs targeting dyskinesia in Parkinson's disease and breathing deficits in Rett syndrome, a devastating orphan disorder. Read more...