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Annotation

Gilmour G, Broad LM, Wafford KA, Britton T, Colvin EM, Fivush A, Gastambide F, Getman B, Heinz BA, McCarthy AP, Prieto L, Shanks E, Smith JW, Taboada L, Edgar DM, Tricklebank MD. In vitro characterisation of the novel positive allosteric modulators of the mGlu(5) receptor, LSN2463359 and LSN2814617, and their effects on sleep architecture and operant responding in the rat. Neuropharmacology . 2013 Jan ; 64(1):224-39. PubMed Abstract

Comments on Paper and Primary News
Comment by:  J B
Submitted 12 October 2012 Posted 13 October 2012
  I recommend this paper

These are promising results for a much needed development in the area of mGluR5 positive allosteric modulators (PAMs) for the treatment of schizophrenia. This paper supplies convincing preclinical evidence that two novel mGluR5 PAMs (LN2463359 and LN2814617) have overcome previous shortfalls of this class of drugs such as agonist activity and solubility issues. Despite the positive results regarding in-vitro characterisation, more studies are required to decipher the lack of effect for reversing amphetamine-induced hyperlocomotion.

In addition to the comparison with haloperidol, I would have liked to see these novel mGluR5 PAMs tested against common second or third generation antipsychotic agents such as clozapine or risperidone (perhaps this is a future direction). Nonetheless, the oral administration route, in combination with the wake-promoting effects and ability to attenuate deficits in operant behaviour induced by NMDAR antagonism, is encouraging.

View all comments by J B

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