Matches in SemOpenAlex for { <https://semopenalex.org/work/W2346530763> ?p ?o ?g. }
- W2346530763 endingPage "24" @default.
- W2346530763 startingPage "10" @default.
- W2346530763 abstract "Efavirenz is highly effective at suppressing HIV-1, and the WHO guidelines list it as a component of the first-line antiretroviral (ARV) therapies for treatment-naïve patients. Though the pharmacological basis is unclear, efavirenz is commonly associated with a risk for neuropsychiatric adverse events (NPAEs) when taken at the prescribed dose. In many patients these NPAEs appear to subside after several weeks of treatment, though long-term studies show that in some patients the NPAEs persist. In a recent study focusing on the abuse potential of efavirenz, its receptor psychopharmacology was reported to include interactions with a number of established molecular targets for known drugs of abuse, and it displayed a prevailing behavioral profile in rodents resembling an LSD-like activity. In this report, we discovered interactions with additional serotonergic targets that may be associated with efavirenz-induced NPAEs. The most robust interactions were with 5-HT3A and 5-HT6 receptors, with more modest interactions noted for the 5-HT2B receptor and monoamine oxidase A. From a molecular mechanistic perspective, efavirenz acts as a 5-HT6 receptor inverse agonist of Gs-signaling, 5-HT2A and 5-HT2C antagonist of Gq-signaling, and a blocker of the 5-HT3A receptor currents. Efavirenz also completely or partially blocks agonist stimulation of the M1 and M3 muscarinic receptors, respectively. Schild analysis suggests that efavirenz competes for the same site on the 5-HT2A receptor as two known hallucinogenic partial agonists (±)-DOI and LSD. Prolonged exposure to efavirenz reduces 5-HT2A receptor density and responsiveness to 5-HT. Other ARVs such as zidovudine, nevirapine and emtricitabine did not share the same complex pharmacological profile as efavirenz, though some of them weakly interact with the 5-HT6 receptor or modestly block GABAA currents." @default.
- W2346530763 created "2016-06-24" @default.
- W2346530763 creator A5005398214 @default.
- W2346530763 creator A5032250533 @default.
- W2346530763 creator A5047308650 @default.
- W2346530763 creator A5071694143 @default.
- W2346530763 creator A5076963133 @default.
- W2346530763 creator A5090854453 @default.
- W2346530763 date "2016-08-01" @default.
- W2346530763 modified "2023-10-16" @default.
- W2346530763 title "Molecular mechanisms of serotonergic action of the HIV-1 antiretroviral efavirenz" @default.
- W2346530763 cites W1573555503 @default.
- W2346530763 cites W1805404385 @default.
- W2346530763 cites W1966245088 @default.
- W2346530763 cites W1966532173 @default.
- W2346530763 cites W1971729817 @default.
- W2346530763 cites W1972939692 @default.
- W2346530763 cites W1974233995 @default.
- W2346530763 cites W1988441237 @default.
- W2346530763 cites W1988444307 @default.
- W2346530763 cites W1994603066 @default.
- W2346530763 cites W1997058647 @default.
- W2346530763 cites W2003581883 @default.
- W2346530763 cites W2004949728 @default.
- W2346530763 cites W2004954392 @default.
- W2346530763 cites W2005165581 @default.
- W2346530763 cites W2005845260 @default.
- W2346530763 cites W2009134620 @default.
- W2346530763 cites W2011912864 @default.
- W2346530763 cites W2017659594 @default.
- W2346530763 cites W2019365078 @default.
- W2346530763 cites W2019543871 @default.
- W2346530763 cites W2019632295 @default.
- W2346530763 cites W2020291589 @default.
- W2346530763 cites W2022578595 @default.
- W2346530763 cites W2026297831 @default.
- W2346530763 cites W2031090984 @default.
- W2346530763 cites W2031496840 @default.
- W2346530763 cites W2039664014 @default.
- W2346530763 cites W2039994228 @default.
- W2346530763 cites W2042867111 @default.
- W2346530763 cites W2043746918 @default.
- W2346530763 cites W2043937374 @default.
- W2346530763 cites W2047066766 @default.
- W2346530763 cites W2048509938 @default.
- W2346530763 cites W2048801917 @default.
- W2346530763 cites W2049647348 @default.
- W2346530763 cites W2055141742 @default.
- W2346530763 cites W2058175142 @default.
- W2346530763 cites W2063194215 @default.
- W2346530763 cites W2069027411 @default.
- W2346530763 cites W2072376676 @default.
- W2346530763 cites W2073331782 @default.
- W2346530763 cites W2074491668 @default.
- W2346530763 cites W2075748132 @default.
- W2346530763 cites W2079825367 @default.
- W2346530763 cites W2081686997 @default.
- W2346530763 cites W2083359555 @default.
- W2346530763 cites W2086063725 @default.
- W2346530763 cites W2087011686 @default.
- W2346530763 cites W2091302209 @default.
- W2346530763 cites W2093607705 @default.
- W2346530763 cites W2099291117 @default.
- W2346530763 cites W2099746597 @default.
- W2346530763 cites W2099797657 @default.
- W2346530763 cites W2102696271 @default.
- W2346530763 cites W2106737113 @default.
- W2346530763 cites W2111013752 @default.
- W2346530763 cites W2113425599 @default.
- W2346530763 cites W2116410566 @default.
- W2346530763 cites W2118259237 @default.
- W2346530763 cites W2120918936 @default.
- W2346530763 cites W2121372715 @default.
- W2346530763 cites W2124431940 @default.
- W2346530763 cites W2128419036 @default.
- W2346530763 cites W2136936499 @default.
- W2346530763 cites W2138346169 @default.
- W2346530763 cites W2140774335 @default.
- W2346530763 cites W2146726034 @default.
- W2346530763 cites W2148759492 @default.
- W2346530763 cites W2151272627 @default.
- W2346530763 cites W2155552540 @default.
- W2346530763 cites W2161558889 @default.
- W2346530763 cites W2162959287 @default.
- W2346530763 cites W2163797688 @default.
- W2346530763 cites W2164339448 @default.
- W2346530763 cites W2168256117 @default.
- W2346530763 cites W2168363131 @default.
- W2346530763 cites W2168836105 @default.
- W2346530763 cites W2170494228 @default.
- W2346530763 cites W2221959480 @default.
- W2346530763 cites W2259965413 @default.
- W2346530763 cites W2266635801 @default.
- W2346530763 cites W2316311942 @default.
- W2346530763 cites W2334561380 @default.
- W2346530763 cites W2345404754 @default.
- W2346530763 cites W2398650533 @default.
- W2346530763 cites W2411264600 @default.