# 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.