Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Sep 2012
ReviewTargeting TRPV1 for pain relief: limits, losers and laurels.
With 336 reviews, the capsaicin receptor TRPV1 arguably represent today's most extensively reviewed analgesic target. TRPV1 is strategically located at the peripheral terminals of primary sensory neurons where pain is generated. TRPV1 as a target for analgesic drugs has been validated in preclinical studies. ⋯ Since its discovery in 1997, TRPV1 has run the gamut from excitement to disappointment to cautious optimism. Topical capsaicin has been disappointing for pain relief. By contrast, intrathecal resiniferatoxin is currently undergoing clinical trials in patients with intractable cancer pain. Some of the small-molecule TRPV1 antagonists have successfully passed Phase I safety and tolerability studies in healthy volunteers into Phase II studies to access efficacy in patients. Others showed worrisome unforeseen adverse effects, most important, hyperthermia and impaired noxious heat sensation. We conclude that TRPV1 blockade and desensitization are two promising, complimentary approaches for pain relief. Despite the roadblocks, TRPV1 remains a powerful tool in pain research and a promising therapeutic target.
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Expert Opin Investig Drugs · Sep 2012
EditorialPregabalin in clinical psychiatry and addiction: pros and cons.
Pregabalin acts as a presynaptic modulator of excitatory neurotransmitter release, binding to the α²-δ subunit protein of voltage-gated calcium channels. Pregabalin use is becoming widespread in the psychiatric scenario. Data are encouraging, with some good evidence for efficacy in anxious spectrum, benzodiazepine abuse/dependence, and alcoholism. The abuse potential, however, is an issue that should be taken into account, mostly in subjects at risk for developing substance/alcohol misuse.