Experimental and clinical psychopharmacology
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Exp Clin Psychopharmacol · Feb 2006
ReviewLow efficacy opioids: implications for sex differences in opioid antinociception.
It is becoming increasingly evident that the sex of an organism is a critical determinant of responsiveness to opioid analgesics. However, the factors that determine the magnitude and direction of sex differences in opioid antinociception have not been fully elucidated. One factor that has received attention is the relative efficacy of the opioid. ⋯ These factors may interact with opioid efficacy to determine the specific conditions under which sex differences are observed. The testing of low efficacy opioids by other laboratories and under other experimental conditions will determine the extent to which this variable affords a strategic research tool. The potential utility of low efficacy opioids in other domains of behavioral pharmacology is also discussed.
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Exp Clin Psychopharmacol · Feb 2006
Adverse effects of gabapentin and lack of anti-allodynic efficacy of amitriptyline in the streptozotocin model of painful diabetic neuropathy.
Amitriptyline and gabapentin are the primary treatments for painful diabetic neuropathy (PDN), and it is clear that they produce beneficial effects, but there are questions about these treatments that have not been adequately addressed. For example, although there is a growing consensus that the therapeutic effects of amitriptyline in pain patients are independent of its effects on mood, it is not clear that amitriptyline has specific and direct effects on pain. There is also a fairly broad consensus that gabapentin is safe and well tolerated, but the side-effect profile of gabapentin has not been adequately assessed in pain populations. ⋯ Gabapentin produced robust anti-allodynic effects but also produced deficits in tests of motor/ambulatory and cognitive functions. The present experiments suggest that the beneficial effects of amitriptyline in PDN may not be a result of anti-allodynic efficacy and that gabapentin produces robust anti-allodynic effects but may also produce significant motor and cognitive deficits even at or near the lowest effective doses. These findings challenge the consensus opinions about these primary treatments for PDN and suggest that their therapeutic and adverse effects should be explored further in pain patients.