way-100635 way-100635 way-100635 is a piperazine drug and research chemical widely used in scientific studies. it was originally believed to act as a selective 5-ht1a receptor antagonist, but subsequent research showed that it also acts as potent full agonist at the d4 receptor. it is sometimes referred to as a silent antagonist at the former receptor. it is closely related to way-100135. way-100635identifiers iupac name n-ethyl]-n-(2-pyridyl)cyclohexanecarboxamide cas number146714-97-8 ypubchem cid5684iuphar/bps80chemspider5482 nunii8s48p899nechemblchembl31354 ncomptox dashboard (epa)dtxsid20167467 chemical and physical dataformulac25h34n4o2molar mass422.573 g·mol−13d model (jsmol)interactive image smiles coc1=cc=cc=c1n2ccn(cc2)ccn(c3=cc=cc=n3)c(=o)c4ccccc4 inchi inchi=1s/c25h34n4o2/c1-31-23-12-6-5-11-22(23)28-18-15-27(16-19-28)17-20-29(24-13-7-8-14-26-24)25(30)21-9-3-2-4-10-21/h5-8,11-14,21h,2-4,9-10,15-20h2,1h3 nkey:sbpriagpyfycrt-uhfffaoysa-n n ny (what is this?) (verify) in light of its only recently discovered dopaminergic activity, conclusions drawn from studies that employed way-100635 as a selective 5-ht1a antagonist may need to be re-evaluated. human pet studies in human pet studies way-100635 shows high binding in the cerebral cortex, hippocampus, raphe nucleus and amygdaloid nucleus, while lower in thalamus and basal ganglia. one study described a single case with relatively high binding in the cerebellum. in relating its binding to subject variables one swedish study found way-100635 binding in raphe brain region correlating with self-transcendence and spiritual acceptance personality traits. way-100635 binding has also been assessed in connection with clinical depression, where there has been disagreement about the presence and direction of the 5-ht1a receptor binding. in healthy subjects way-100635 binding has been found to decline with age, — though not all studies have found this relationship. human way-100635 binding neuroimaging studies (patients compared to healthy control subjects). whatresultsubjectsref. age global decrease and particularly in parietal cortex and dorsolateral prefrontal cortex 19 age no correlation found 61 age no correlation detected 25 sex higher binding in females 25 tci self-transcendence and spiritual acceptance personality traits positive correlation in raphe region 15 males lifetime aggression negative correlation 25 madam binding potential (serotonin transporter binding) positive correlation in the raphe nuclei and hippocampus 12 males genetic variationresultsubjectsref. htr1a.(-1018)c>g polymorphism no difference found 35 sert.5-httlpr polymorphism lower binding in "all brain regions" for ss or sl genotypes compared to ll 35 diseaseresultsubjectsref. depressive (with primary, recurrent, familial mood disorders) reduction in raphe nucleus and mesiotemporal cortex 12+8 major depressive disorder (medicated and unmedicated) reduction in "many of the regions examined" 25+18 panic disorder in treated and untreated patients reducing in binding in raphe in both treated and untreated. reduced binding in global postsynaptic regions for untreated, while no or little reduction for treated. 9+7+19 alzheimer disease decrease in right medial temporal cortex 10+10 radioligands labeled with the radioisotope carbon-11 it is used as a radioligand in positron emission tomography (pet) studies to determine neuroreceptor binding in the brain. way-100635 may be labeled in different ways with carbon-11: as way-100635 or way-100635, with way-100635 regarded as "far superior". labeled with tritium way-100635 may also be used in autoradiography. way-100635 has higher 5-ht1a affinity than 8-oh-dpat. other actions way-100635 has also been found to increase the analgesic effects of opioid drugs in a dose-dependent manner, in contrast to 5-ht1a agonists such as 8-oh-dpat which were found to reduce opioid analgesia. however, since 5-ht1a agonists were also found to reduce opioid-induced respiratory depression and way-100635 was found to block this effect, it is likely that 5-ht1a antagonists might worsen this side effect of opioids. paradoxically, chronic administration of the very high efficacy 5-ht1a agonist befiradol results in potent analgesia following an initial period of hyperalgesia, an effect most likely linked to desensitisation and/or downregulation of 5-ht1a receptors (i.e. analogous to a 5-ht1a antagonist-like effect). as with other 5-ht1a silent antagonists such as uh-301 and robalzotan, way-100635 can also induce a head-twitch response in rodents.