Modulation of NMDA and dopaminergic neurotransmissions by sigma ligands: Possible implications for the treatment of psychiatric disorders

Sigma (sigma) receptors, improperly classified as belonging to the opiate receptor family when discovered in 1976, were subsequently confused with phencyclidine binding sites for several years. It's only recently, with the emergence of new selective ligands that their functional significance could be meaningfully addressed. Several subtypes of sigma receptors are present in high densities in the limbic structures as well as in motor-related areas of the CNS. Different lines of evidence suggest that a major role for sigma receptors might be to regulate the activity of the glutamatergic system via the modulation one of its subtype of receptor, the NMDA receptor. This modulation of the glutamatergic system could in turn interfere with the dopaminergic neurotransmission with which, however, sigma ligands could also interact directly.