Re: Pharmacotherapy of Depression-recent advances

[Guest guest]

Respected members,

Aglomelatine – A melatonergic antidepressant

• Agomelatine is a novel anti-depressant with melatonergic( MT1 /MT2) agonist and serotonin 5HT2C antagonist property. It is available in Europe.

• Phase shift hypothesis is one of The hypothesis for the pathogenesis of major depression.

• Stimulation of melatonergic receptor in the suprachaismatic nucleus of hypothalamus by agomelatine leads to the restoration of circadian rhythm, hence it is referres as `rhythm stabilising antidepressant'.

• It also binds to the serotonergic 5HT2C receptors and secondarily increase norepineprine and dopamine levels..

mGlu2/3 receptor agonists

• mGlu2/3 receptor agonists are considered to exert their effects by acting on the glutamatergic, dopaminergic, and 5-HTergic pathways.

• Administration of NMDA receptor antagonists increases glutamate release in the prefrontal cortex, and also elicits working memory dysfunction .

• Thus, it is presumed that NMDA receptor dysfunction in the prefrontal cortex increases glutamate release and, thereby, impairs working memory

Substance P receptor antagonist

• Substance P (SP), an undecapeptide, is abundant both in the periphery and in the CNS, where it is usually co-localised with ,most commonly serotonin (5-HT).

• A role for SP is proposed in the regulation of pain, asthma, psoriasis, inflammatory bowel disease and, in the CNS, emesis, migraine, schizophrenia, depression and anxiety.

• MK 869, a novel SP antagonist, not directly related to monoamine transmitters, has showed efficacy in depression. Its Trials are suspended.

• But Substance P antagonists prospects and implications for future treatments of depression.

Corticotropin releasing hormone antagonist

• Antalarmin is a drug that acts as a CRF-1 antagonist.

• Antalarmin is a non-peptide drug that blocks the CRF-1 receptor, and, as a consequence, reduces the release of ACTH in response to chronic stress.

• This has been demonstrated in animals to reduce the behavioural responses to stressful situations,and it is proposed that antalarmin itself, or more likely newer CRF antagonist drugs still under development, could be useful in the treatment of conditions such as anxiety, depression, and drug addiction.

Also , Omega-3 fatty acid SUPPLEMENTATION ---antidepressant-like effects.

Other drugs

• Lamotrigine – a broad spectrum anti-epileptic

• Quetiapine – a atypical anti-psychotic drug

• Modafinil

• Pramipexole

Regards,

Dr Ankush Gaikwad

Second year resident, Department of Pharmacology

GMC, Nagpur