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The Potential Contribution of Sigma Receptors to Antidepressant Actions

  • Chapter
Antidepressants

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

The origin of the concept of the σ-receptor is closely linked with the unraveling of the complexity of the opiate receptor. The potent effects of the naturally occurring opiates have been recorded since antiquity, but it was only inn the late nineteenth century that the scientific basis for action of the morphine-like opioids was laid. There were several reasons for this development, but undoubtedly the need to produce effective antitussive agents to facilitate the healing of tubercular pulmonary lesions motivated such changes. In addition, the increase in opiate abuse, particulary in the United States, emphasized the need to understand the pharmacological basis of opiate abuse and thereby provide a rational basis for its treatment. An outcome from such studies was the synthesis of several opiate receptor antagonists. One of the first of these was nalorphine, which Lasagna and Beecher (1) demonstrated to have analgesic activity, but which would also precipitate abstinence symptoms in morphine-dependent subjects. Further development of nalorphine as an analgesic was prevented by the dysphoric effects it caused in many subjects. The search for drugs that combined the potent analgesic effect of morphine with a negligible abuse potential eventually led to the synthesis of pentazocine and cyclazocine (2). Again, it was found that the analgesic effects of these drugs were combined with dysphoric effects that were dose-related, the morphine-like effects being most pronounced at low doses and the dysphoric-hallucinogenic effects at high doses. Furthermore, it was found that pentazocine, like nalophine, would precipitate withdrawal in morphine-dependent subjects.

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  1. Laboratory of Neuroscience, National Institutes of Health, Bethesda, MD, USA

    Phil Skolnick

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Leonard, B.E. (1997). The Potential Contribution of Sigma Receptors to Antidepressant Actions. In: Skolnick, P. (eds) Antidepressants. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-474-0_9

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