Analgesic nitrous oxide in neuropsychiatry: past, present and future

We highlight the distinction between analgesic and anesthetic concentrations of nitrous oxide, with special reference to the safety of analgesic nitrous oxide. We present evidence that the gas at analgesic concentrations is an opioid agonist. Its extremely low abuse potential, despite its opioid properties, is discussed with regard to its evanescent action and possible partial agonistic effects, making it the least addictive of all mind-altering addictive substances. The activities of analgesic nitrous oxide make it an almost ideal agent with which to investigate the functions of the opioid system in man. We also discuss its use as a diagnostic and therapeutic agent in neuropsychiatry.     

Discovery and Evaluation of BMS-708163, a Potent,Selective and Orally Bioavailable γ-Secretase Inhibitor

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The road from Santa Rosalia: a faster tempo of evolution in tropical climates

Using an appropriately designed and replicated study of a latitudinal influence on rates of evolution, we test the prediction by K. Rohde [(1992) Oikos 65, 514-527] that the tempo of molecular evolution in the tropics is greater than at higher latitudes. Consistent with this prediction we found tropical plant species had more than twice the rate of molecular evolution as closely related temperate congeners. Rohde's climate-speciation hypothesis constitutes one explanation for the cause of that relationship. This hypothesis suggests that mutagenesis occurs more frequently as productivity and metabolic rates increase toward the equator. More rapid mutagenesis was then proposed as the mechanism that increases evolutionary tempo and rates of speciation. A second possible explanation is that faster rates of molecular evolution result from higher tropical speciation rates [e.g., Bromham, L. & Cardillo, M. (2003) J. Evol. Biol. 16, 200-207]. However, we found the relationship continued to hold for genera with the same number of, or more, species in temperate latitudes. This finding suggests that greater rates of speciation in the tropics do not cause higher rates of molecular evolution. A third explanation is that more rapid genetic drift might have occurred in smaller tropical species populations [Stevens, G. C. (1989) Am. Nat. 133, 240-256]. However, we targeted common species to limit the influence of genetic drift, and many of the tropical species we used, despite occurring in abundant populations, had much higher rates of molecular evolution. Nonetheless, this issue is not completely resolved by that precaution and requires further examination.     

Antidepressants are not drugs of abuse or dependence

There is a view among both the lay and medical audience that antidepressants are addictive. Non-compliance may arise as a result, with fatal consequences in some cases. In spite of the fact that anti-depressants have not proved to be drugs of abuse or dependence, confusion exists in the literature, particularly regarding the definition of the terms misuse and abuse in opioid addicts. Here, antidepressants are used to treat the depressive component of the addictive syndrome and have proved effective. In some instances, however, misuse of antidepressants has been found in methadone-treated addicts, which may be due to an enhancement of the effects of methadone. These effects have led some people to believe, wrongly, that antidepressants are substances of abuse. Our findings, from a review of the literature, show that such use of antidepressants by methadone patients is by definition misuse and not abuse. Further, the known withdrawal symptoms which occasionally follow cessation of anti-depressant therapy are not, on their own, an indication of addictive potential. We therefore conclude that antidepressant drugs are not substances of abuse and dependence.