03 - Novel agents in the making

Novel agents in the making

© SPMM Course Classification by mechanisms of action SSRIs Citalopram, Paroxetine, Fluoxetine, Sertraline and Fluvoxamine, S enantiomer of citalopram

• Escitalopram SNRIs – serotonin and noradrenaline reuptake inhibitor Venlafaxine, Milnacipran, Duloxetine, Sibutramine NARI – Noradrenaline reuptake inhibitor – Reboxetine NDDI – Noradrenaline Dopamine DisInhibitor - Agomelatine NaSSA – Noradrenergic and specific serotonergic antagonist – Mirtazapine and Mianserin DARI – Dopamine reuptake inhibitor - Bupropion RIMA – reversible inhibitor of Monoamine A oxidase - Moclobemide SARI – serotonin antagonist and reuptake inhibitors – Nefazodone, Trazodone.

Novel agents in the making Xanomeline underwent phase 3 trials as a treatment option for schizophrenia. It acts via M1/M4 agonism Xanomeline showed a trend toward improving cognitive function in Alzheimer’s, and produced robust and dose-dependent reductions in psychotic symptoms in AD. In schizophrenia, early trials showed efficacy in both the positive and the negative symptoms along with improvements in verbal learning and short-term memory but, a high degree of gastrointestinal side effects were observed. Ketamine is a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist that has shown rapid antidepressant effects in treatment-resistant depression. Large scale trials are being undertaken currently. Pomaglumetad methionil (LY2140023 monohydrate), a metabotropic glutamate receptor 2/3 agonist, appeared to be a promising agent for sometime as initial phase 2 studies showed promising efficacy against positive and negative symptoms when used as an add-on therapy in schizophrenia. But this result was not replicated in a later study, mostly due to high placebo response. It is devoid of affinity for dopamine receptors.