Life sciences
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Capsaicin, the pungent constituent of chili peppers, represents the paradigm for the capsaicinoids or vanilloids, a family of compounds shown to stimulate and then desensitize specific subpopulations of sensory receptors, including C-polymodal nociceptors, A-delta mechanoheat nociceptors and warm receptors of the skin, as well as enteroceptors of thin afferent fibers. An exciting recent advance in the field has been the finding that resiniferatoxin (RTX), a naturally occurring diterpene containing a homovanillic acid ester, a key structural motif of capsaicin, functions as an ultrapotent capsaicin analog. ⋯ Specific [3H]RTX binding provides the first direct proof for the existence of vanilloid receptors. We expect that the RTX class of vanilloids will promote rapid progress in understanding of vanilloid structure/activity requirements and mechanism.
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Review Comparative Study
Cocaine and central monoaminergic neurotransmission: a review of electrophysiological studies and comparison to amphetamine and antidepressants.
Psychomotor stimulants (e.g. cocaine and amphetamine) and many antidepressants are believed to elicit their psychotropic actions by interacting primarily with central monoaminergic neurons. The acute central neuronal effects of amphetamine and antidepressants have been extensively investigated in rats utilizing extracellular single unit electrophysiological and microiontophoretic techniques in vivo. In recent years the chronic effects of these compounds on the above neuronal systems have also been reported. ⋯ In terms of effects on single monoaminergic neurons, this assumption had gone by untested until two years ago, when the first report of the electrophysiological effects of cocaine on central monoaminergic (locus ceruleus) neurons appeared in the literature (61). This review discusses recent electrophysiological studies with cocaine at the level of single identified monoaminergic neurons and compares such data with that previously reported for amphetamine and antidepressants. In addition to identifying some of the similarities and differences between these compounds, this review also highlights some of the gaps in our knowledge regarding the effects of these drugs on central monoaminergic neurotransmission.
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The literature provides considerable evidence indicating that several, but not all antihistaminics, are indeed analgesic agents and some are analgesic adjuvants as well. Those for which effectiveness is reported includes diphenhydramine, hydroxyzine, orphenadrine, pyrilamine, phenyltoloxamine, promethazine, methdilazine, and tripelennamine. The proposed mechanisms of analgesic action of antihistaminics are reviewed and discussed. ⋯ The evidence for a role for norepinephrine and dopamine and the effects of antihistaminics on them are less well established. Still other pathways have been proposed. A greater understanding of pain mechanisms will aid in elucidating the role of antihistaminics in analgesia.