Opioid receptor kappa sigma

Iwamoto, E.T. Locomotor activity and antinociception after putative mu, kappa and sigma opioid receptor agonists in the rat Influence of dopaminergic agonists and antagonists. J Pharmacol Exp Ther 217 451-460, 1981. 

Opioid receptors comprise a heterogenous group that can be divided into at least four biochemically and topographically distinct sub-types, designated mu, kappa, sigma, and delta. Martin et al. ... 

In rodents, PCP produces not only ataxia, but also stereotyped behavior and hyperactivity. The PCP-induced stereotyped behavior is thought to be due to changes in serotonergic and dopaminergic systems (Nabeshima et al. 1983 Martin et al. 1979 Sturgeon et al. 1981). It is not known whether PCP receptors mediate PCP-induced hyperactivity or stereotyped behavior or even the effect on neurotransmitter systems. It is also possible that mu, kappa, or sigma opioid receptors are involved (Castellani et al. 1982). 

In 1976 Martin proposed the theory that there are three subtypes of opioid receptor on the basis of behavioural studies using a chronic spinal dog model which revealed that the opioids morphine (mu) (1), ketazocine (kappa) (2) and A-allylnormetazocine (SKF 10047) (4) (sigma) had different effects on respiration, heart rate and locomotor activity [13]. Furthermore, these ligands were unable to replace each other to prevent withdrawal symptoms in dogs that had been chronically treated with one of the compounds. 

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. 

Dooley, C.T., Ny, P., Bidlack, J.M. and Houghten, R.A. Selective ligands for the sigma, delta, and kappa opioid receptors identified from a single mixture based tetrapeptide positional scanning combinatorial library./. Biol. Chem., 1998,273, 18848-1 8856. 

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. 

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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