In light of itsdopaminergic activity, conclusions drawn from studies that employ WAY-100635 as a selective 5-HT1A antagonist may need to be re-evaluated.[5]
In relating its binding to subject variables one Swedish study found WAY-100635 binding inraphe brain region correlating withself-transcendence and spiritual acceptancepersonality traits.[8]WAY-100635 binding has also been assessed in connection withclinical depression, where there has been disagreement about the presence and direction of the 5-HT1A receptor binding.[9]In healthy subjects WAY-100635 binding has been found to decline withage,[10]— though not all studies have found this relationship.[11][12]
Human WAY-100635 binding neuroimaging studies (patients compared to healthy control subjects).
Reducing in binding inraphe in both treated and untreated. Reduced binding in global postsynaptic regions for untreated, while no or little reduction for treated.
WAY-100635 has also been found to increase the analgesic effects ofopioid drugs in a dose-dependent manner, in contrast to 5-HT1A agonists such as8-OH-DPAT which were found to reduce opioid analgesia.[23][24] However, since 5-HT1A agonists were also found to reduce opioid-inducedrespiratory depression and WAY-100635 was found to block this effect,[25] it is likely that 5-HT1A antagonists might worsen this side effect of opioids. Paradoxically, chronic administration of the very high efficacy 5-HT1A agonistbefiradol results in potent analgesia following an initial period ofhyperalgesia, an effect most likely linked to desensitisation and/or downregulation of 5-HT1A receptors (i.e. analogous to a 5-HT1A antagonist-like effect).[26][27][28] As with other 5-HT1A silent antagonists such asUH-301 androbalzotan, WAY-100635 can also induce ahead-twitch response in rodents.[29]
^Marona-Lewicka D, Nichols DE (February 2009). "WAY 100635 produces discriminative stimulus effects in rats mediated by dopamine D(4) receptor activation".Behavioural Pharmacology.20 (1):114–118.doi:10.1097/FBP.0b013e3283242f1a.PMID19179855.S2CID43332577.
^Fletcher A, Forster EA, Bill DJ, Brown G, Cliffe IA, Hartley JE, et al. (1996). "Electrophysiological, biochemical, neurohormonal and behavioural studies with WAY-100635, a potent, selective and silent 5-HT1A receptor antagonist".Behavioural Brain Research.73 (1–2):337–353.doi:10.1016/0166-4328(96)00118-0.PMID8788530.S2CID18229202.
^Chemel BR, Roth BL, Armbruster B, Watts VJ, Nichols DE (October 2006). "WAY-100635 is a potent dopamine D4 receptor agonist".Psychopharmacology.188 (2):244–251.doi:10.1007/s00213-006-0490-4.PMID16915381.S2CID24194034.
^abRabiner EA, Messa C, Sargent PA, Husted-Kjaer K, Montgomery A, Lawrence AD, et al. (March 2002). "A database of [(11)C]WAY-100635 binding to 5-HT(1A) receptors in normal male volunteers: normative data and relationship to methodological, demographic, physiological, and behavioral variables".NeuroImage.15 (3):620–632.doi:10.1006/nimg.2001.0984.PMID11848705.S2CID42080193.
^abcdParsey RV, Oquendo MA, Simpson NR, Ogden RT, Van Heertum R, Arango V, Mann JJ (November 2002). "Effects of sex, age, and aggressive traits in man on brain serotonin 5-HT1A receptor binding potential measured by PET using [C-11]WAY-100635".Brain Research.954 (2):173–182.doi:10.1016/S0006-8993(02)03243-2.PMID12414100.S2CID20650203.
^Lundberg J, Borg J, Halldin C, Farde L (December 2007). "A PET study on regional coexpression of 5-HT1A receptors and 5-HTT in the human brain".Psychopharmacology.195 (3):425–433.doi:10.1007/s00213-007-0928-3.PMID17874074.S2CID22272672.
^Lanctôt KL, Hussey DF, Herrmann N, Black SE, Rusjan PM, Wilson AA, et al. (October 2007). "A positron emission tomography study of 5-hydroxytryptamine-1A receptors in Alzheimer disease".The American Journal of Geriatric Psychiatry.15 (10):888–898.doi:10.1097/JGP.0b013e3180488325.PMID17567932.
^Pike VW, McCarron JA, Lammerstma AA, Hume SP, Poole K, Grasby PM, et al. (September 1995). "First delineation of 5-HT1A receptors in human brain with PET and [11C]WAY-100635".European Journal of Pharmacology.283 (1–3):R1 –R3.doi:10.1016/0014-2999(95)00438-Q.PMID7498295.
^Pike VW, McCarron JA, Lammertsma AA, Osman S, Hume SP, Sargent PA, et al. (April 1996). "Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11 C]WAY-100635".European Journal of Pharmacology.301 (1–3):R5 –R7.doi:10.1016/0014-2999(96)00079-9.PMID8773468.
^Hume SP, Ashworth S, Opacka-Juffry J, Ahier RG, Lammertsma AA, Pike VW, et al. (December 1994). "Evaluation of [O-methyl-3H]WAY-100635 as an in vivo radioligand for 5-HT1A receptors in rat brain".European Journal of Pharmacology.271 (2–3):515–523.doi:10.1016/0014-2999(94)90813-3.PMID7705452.
^Burnet PW, Eastwood SL, Harrison PJ (June 1997). "[3H]WAY-100635 for 5-HT1A receptor autoradiography in human brain: a comparison with [3H]8-OH-DPAT and demonstration of increased binding in the frontal cortex in schizophrenia".Neurochemistry International.30 (6):565–574.doi:10.1016/S0197-0186(96)00124-6.PMID9152998.S2CID21135585.
^Berrocoso E, De Benito MD, Mico JA (July 2007). "Role of serotonin 5-HT1A and opioid receptors in the antiallodynic effect of tramadol in the chronic constriction injury model of neuropathic pain in rats".Psychopharmacology.193 (1):97–105.doi:10.1007/s00213-007-0761-8.PMID17393145.S2CID21898521.
^Sahibzada N, Ferreira M, Wasserman AM, Taveira-DaSilva AM, Gillis RA (February 2000). "Reversal of morphine-induced apnea in the anesthetized rat by drugs that activate 5-hydroxytryptamine(1A) receptors".The Journal of Pharmacology and Experimental Therapeutics.292 (2):704–713.PMID10640309.
^Bardin L, Assié MB, Pélissou M, Royer-Urios I, Newman-Tancredi A, Ribet JP, et al. (March 2005). "Dual, hyperalgesic, and analgesic effects of the high-efficacy 5-hydroxytryptamine 1A (5-HT1A) agonist F 13640 [(3-chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl}piperidin-1-yl]methanone, fumaric acid salt]: relationship with 5-HT1A receptor occupancy and kinetic parameters".The Journal of Pharmacology and Experimental Therapeutics.312 (3):1034–1042.doi:10.1124/jpet.104.077669.PMID15528450.S2CID42446435.
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