Sigma receptors depression

There are various opioid receptors the three major classes of opioid receptors are mu (p), delta (5) and kappa (k) receptors. The p, receptor is the principal pain-modulating site in the CNS, mediating the action of morphine. There is considerable interest in the K receptor, which mediates a sedating analgesia with decreased addiction liability and respiratory depression and which allows for some structural flexibility. Unfortunately, the K receptor seems to be coupled to the sigma (a) receptor, which is implicated in psychotomimetic and dysphoric side effects. 

Actions at sigma 1 receptors may explain potential advantages of fluvoxamine for psychotic depression and delusional depression... 

Opiate effects are mediated via multiple opioid receptors such as the mu, kappa, delta, and sigma. The mu receptors mediate analgesia, euphoria, physical dependence, and depression of ventilation. 

A. PCP and ketamine are dissociative anesthetics that produce generalized loss of pain perception with little or no depression of airway reflexes or ventilation. Psychotropic effects are mediated through several mechanisms, including stimulation of sigma opioid receptors inhibition of reuptake of dopamine, norepinephrine, and serotonin and blocking of potassium conductance. 

Four principal opioid receptor subtypes, designated as mu, kappa, delta, and sigma, have been characterized [1,2]. A newer receptor classification system utilizes labels OPRj, OPR and OPR, which correspond to mu, kappa, and delta receptors respectively [1,3,8]. Mu receptors (OPR ) mediate supraspinal analgesia, as well as respiratory depression, nausea and vomiting, miosis and bowel hypomotil-ity. Mu receptors also mediate euphoria and physical and psychological dependence, and are responsible for the increased release of prolactin and growth hormone [1,2]. 

Hydromorphone binds to mu and delta opiod receptors in the central nervous system. It has no effect at the kappa, sigma, or epsilon opioid receptors. Activity at the mu receptors causes analgesia, but also miosis, urinary retention, constipation, hyperthermia, and euphoria. Other side effects such as respiratory depression, pruritus, nausea, vomiting, and development of tolerance are due to binding at both mu and delta receptors. Hydromorphone, unlike other opioids, also has a direct depressant effect on the respiratory brainstem center and the cough center in the medulla. 

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