Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arousal and maintenance of a wake state is dependent on the hypothalamic hypocretin/orexin system. We found that hypocretin neurons are depressed by opiates, drugs of abuse that reduce cognitive alertness. Met-enkephalin (mENK), an endogenous opioid, and exogenous opiates such as morphine inhibited the hypocretin system by direct actions on the cell body that include reduced spike frequency, hyperpolarization, increased G-protein-coupled inwardly rectifying K(+) channel current, and attenuated calcium current, and indirectly through reducing excitatory synaptic tone by a presynaptic mechanism. CTAP (H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH(2)) and naloxone, antagonists of mu-opioid receptors, blocked mu agonist actions. In the absence of exogenous opioids, mu receptor antagonists enhanced activity of the hypocretin system, suggesting ongoing inhibition by endogenous receptors. Morphine pretreatment attenuated subsequent excitatory responses to hypocretin, suggesting a long-lasting depression caused by opiate exposure. Chronic exposure to morphine reduced subsequent responses to morphine and to mENK, but increased the response to opioid receptor antagonists. Together, these data are consistent with the view that the hypocretin system may be an important direct target for drugs of abuse, including opiates, that induce sedation and mental lethargy.
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PMID:Mu-opioid receptor-mediated depression of the hypothalamic hypocretin/orexin arousal system. 1833 11

Fentanyl is a potent synthetic opioid used as a narcotic analgesic supplement in general and regional anesthesia as well as in management of persistent, severe chronic pain. Alarming epidemiological and forensic medicine reports, accumulated mainly during the last two decades, point to a growing increase in illicit use of fentanyl, mainly in North America and Europe. Toxicological data indicates that fentanyl use is inextricably linked with polydrug use. There are two main sources of fentanyl on the "recreational" drug market. First, the most common, combines illicitly manufactured fentanyl from clandestine sources. The drug is often mixed up with heroin ("fake heroin") to increase its potency at a little cost, or included in cocaine products. It can also be mixed into and sold as oxycodone-, hydrocodone- or alprazolam-containing tablets. The other way to gain fentanyl is through the diversion of fentanyl-containing medicines, especially transdermal patches (FTPs). Fentanyl extracted from FTP can be administered intravenously, insufflated or inhaled after volatilization. The drug can also be delivered by oral or transmucosal application of the whole patch, or by rectal insertion. The most common overdose symptoms are coma, lethargy, respiratory depression and arrest. Although naloxone, an opioid receptor antagonist, is the standard drug for fentanyl overdose rescue, attempts to revive patients with naloxone could be unsuccessful, due to the rapid onset of fentanyl's action. As the fentanyl problem is constantly growing, there is an urgent need for new, effective harm-reduction strategies and technologies, as well as overdose maintenance.
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PMID:Abuse of fentanyl: An emerging problem to face. 2990 99