Name:	SGS-742
Other Names:	CGP-36742, DVD-742
Therapy Types:	Pharmacological
Mechanisms:	GABAB receptor antagonist.
Development Status:	investigational in U.S.
FDA Phase:	Discontinued
Primary Medical Role:	Not used in any other applications. Target is to use SGS- 742 as a therapy for mild cognitive impairment (MCI) and AD. Activation of the GABAB receptors is known to inhibit memory/learning in certain animal models. It is believed that GABAB antagonists would reverse this effect. GABAB receptor antagonists could disinhibit somatostatin release, which would lead to increased NMDA receptor activity, which is thought to be an important contributor to memory and learning.
Role in Alzheimer's Disease:	GABA receptors are known to inhibit learning in certain animal models. SGS-742 is a GABAB receptor antagonist that is thought to indirectly effect NMDA receptors, and therefore potentially helping memory formation/retention and learning. Some new evidence has also shown that SGS-742 may reduce the expression or activation of transcription factors believed to act as memory suppressors.
Pharmacological Role:	SGS-742 binds selectively to GABAB receptors, and reduces the inhibitory effects of this receptor. Therefore, it essentially disinhibits the targets of GABA inhibition, some of which are implicated in memory and learning processes.
Contraindications:	Impaired renal function
Side Effects:	dizziness, headache and fatigue
Evidence pro its efficacy:	SGS-742 reduced learning deficits induced by baclofen and scopolamine in rats (measured through the Morris Water Maze). In addition, motor incoordination was also found to be decreased after an application of the drug. SGS-742 was found to out-perform donepezil, an acetylcholinesterase inhibitor and AD therapeutic, in a number of different learning paradigms, and was also found to improve spatial memory. Cognitive performance in rats, mice and rhesus monkeys was also improved following SGS-742 administration.
Companies:	Novartis Pharmaceuticals Corporation, Saegis Pharmaceuticals, Inc.
Notes:	Phase II clinical trial NCT00093951 was completed and there is no further clinical testing planned. This record updated Dec 22, 2008.

References

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