Disease relevance of Lopac-W-108

• 6. WAY-100635 (I.V. or intra-cisternally) also reversed bradycardia, hypotension and the decrease in phrenic nerve activity evoked by the I.V. application of 8-OH-DPAT (42 microg kg(-1)) [1].
• 8-OH-DPAT-induced hypothermia was blocked by the 5-HT(1A) antagonist WAY-100635 [2].
• This finding shows that WAY-100635 has the potency to enhance lordosis behavior acutely in female rats with a low estrous state [3].
• However, WAY-100635 and SB-269970 treatment attenuated the drop in Tb in response to hypoxia [4].
• In contrast to the effects observed with the agonists, the inverse agonist WAY 100635 appeared to enhance haloperidol-induced catalepsy in both tests, in agreement with earlier findings [5].

Psychiatry related information on Lopac-W-108

• In experiment 2, 8-OHDPAT in the low dose range inhibited locomotor activity and this effect was reversed by co-administration of WAY 100635 [6].
• METHODS: The social interaction test of anxiety was used to investigate the effects of a range of doses of (-)-nicotine (2.5-4000 ng) following DRN infusion, and whether co-administration of the specific 5-HT1A receptor antagonist WAY 100635 could antagonise the anxiolytic action of nicotine [7].
• A dose of 0.1 mg/kg WAY 100635 to AMPA-lesioned rats improved their choice accuracy but did not shorten correct response latencies [8].
• OBJECTIVE: This study compares Long-Evans rats and squirrel monkeys to examine the hypothesis that low doses of the 5-HT(1A) selective agonists, 8-OH-DPAT and alnespirone, will preferentially increase, and at higher doses decrease alcohol drinking, and whether these effects can be antagonized by WAY 100635 [9].
• Increased REM sleep after intra-dorsal raphe nucleus injection of flesinoxan or 8-OHDPAT: prevention with WAY 100635 [10].

High impact information on Lopac-W-108

• In addition, pretreatment with GR 127935, but not with the 5-HT1A antagonist WAY 100635, prevented the effects of both 5-HT1B agonists [11].
• Because 5-HT1A receptor activation hyperpolarizes and inhibits CA3 pyramidal neurons in the dorsal hippocampus, we determined, using in vivo extracellular recording, whether the selective 5-HT1A receptor antagonist WAY 100635 could disinhibit these neurons [12].
• This inhibitory effect was antagonized by WAY-100635 and the prior inactivation of 5-HT1A receptors in rats and was absent in mice lacking 5-HT1A receptors [13].
• As a positive control, the effect of the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n)-propil-aminotetraline (8-OH-DPAT; 0.0625, 0.125, 0.25 and 0.5 mg/kg) alone or in combination with WAY 100635 (0.5 and 1.0 mg/kg) was analyzed in the FST [14].
• In contrast, (+/-)-pindolol blocked Prx-induced decreases in the immobility time while WAY-100635 had no effect in both genotypes [15].

Chemical compound and disease context of Lopac-W-108

• 2. Intracisternal administration of the 5-HT1A receptor antagonists WAY-100635 (100 microg kg(-1)) and (-)pindolol (100 microg kg(-1)) significantly reduced the smoke-induced bradycardia, attenuated the pressor response and in the case of (-)pindolol, sympathetic nerve activity [16].
• Depletion of 5-HT abolished the enhancement by WAY 100635 of catalepsy induced by low doses of the antipsychotics nemonapride and raclopride, in agreement with the hypothesis that WAY 100635 enhances catalepsy by blocking tonic 5-HT(1A) receptor activation [17].
• Pre-treatment with the dopamine, D(2) antagonist, haloperidol (1 mg/kg) and sulpiride (30 mg/kg) had a similar effect in blocking the hypothermia as WAY 100635, suggesting a role for dopamine D(2) receptors in the response [18].
• The selective 5-HT1A receptor antagonist WAY 100635 (0.15 mg/kg), attenuated the hypothermia induced by the partial agonists, ipsapirone (10 mg/kg) and eltoprazine (10 mg/kg) [19].
• In the sensitive (type A) monkeys WAY 100635 blocked the diethylpropion-induced increase in locomotor activity, while not affecting anxiogenic-like behavioral responses or the suppression of bodycare activities [20].

Biological context of Lopac-W-108

• The impairment of PA caused by PCA was attenuated by WAY 100635 and (-)-pindolol, suggesting an involvement of the 5-HT1A receptor [21].
• In addition, administration of WAY-100635 potentiated the learning-specific increase in the hippocampus of phospho-CaMKII, Ca(2+)-independent CaMKII activity, as well as the phosphorylation of either the CaMKII or the PKA site on the AMPA receptor GluR1 subunit [22].
• In CA1 pyramidal cells, hyperpolarization induced by 50 nM 5-CT was also antagonized by WAY 100635 (IC50 = 0.80 nM, apparent KB= 0.28 nM) [23].
• However, as this inhibition occurred at the highest dose of WAY-100635, which also caused a fall in arterial blood pressure; this effect is considered to be due to blockade of alpha(1)-adrenoceptors not 5-HT(1A) receptors [24].
• However, the same dose of WAY-100635 given i.v. had no effect on this reflex bronchoconstriction [25].

Anatomical context of Lopac-W-108

• WAY-100635 antagonist-induced plasticity of 5-HT receptors: regulatory differences between a stable cell line and an in vivo native system [26].
• In contrast, paroxetine (5 mg/kg s.c.) increased Arc mRNA after pre-treatment with WAY 100635 (0.3 mg/kg s.c.). This increase was apparent in cortical regions (frontal, parietal and cingulate) and caudate nucleus but was absent in hippocampus (CA1) [27].
• WAY-100635 was tested at low doses (0.03-0.3 mg/kg), which antagonize somatodendritic 5-HT(1A) autoreceptors in the raphe nuclei, and at a higher dose (1 mg/kg), which completely blocks postsynaptic 5-HT(1A) receptors [28].
• The effect of loxapine (0.3 mg/kg) on DA release in the prefrontal cortex was attenuated by WAY 100635 (0.2 mg/kg), a 5-HT(1A) antagonist, as is the case for other atypical APDs [29].
• The D2/D3 antagonist raclopride partly inhibited the binding of [11C]RGH-1756 in several brain areas, including the striatum, mesencephalon and neocortex, whereas the 5HT(1A) antagonist WAY-100635 had no evident effect on [11C]RGH-1756 binding [30].

Associations of Lopac-W-108 with other chemical compounds

• The effect of CP-93,129 was prevented by SB-224289, but not by WAY-100635, selective 5-HT1B and 5-HT1A receptor antagonists, respectively [31].
• In controls, as well as in rats receiving a lithium diet for 3 days, the administration of WAY 100635 (25-100 microg/kg, IV) did not modify the firing activity of dorsal hippocampus CA(3) pyramidal neurons [32].
• Also, the perfusion of 100 microM WAY-100635 for 2 h inhibited partly the reduction of 5-HT release evoked by the systemic administration of 8-OH-DPAT (0.1 mg kg(-1)) [33].
• However, fluoxetine suppressed EEG synchronization in the alpha (8-12 Hz) band when administered concurrently with the 5-HT(1A) receptor antagonist WAY 100635 (0.5 mg/kg) [34].
• The effect of 10 mg/kg citalopram was potentiated by WAY-100635 in the frontal cortex but not in the dorsal hippocampus [35].

Gene context of Lopac-W-108

• Potentiation by 5-HT and R-DPAT of mitogen-activated cell survival, S phase transition, and nuclear localization of NF-kappaB, as well as inhibition of apoptosis, were all reversed by the selective 5-HT(1A) receptor antagonist WAY-100635 [36].
• The effectiveness with which M100907 antagonizes the behavioral actions of this compound, coupled with the lack of significant antagonist effects of WAY-100635, strongly suggests that the 5-HT 2A receptor is an important site of action for 5-MeO-DIPT, despite its apparent in vitro selectivity for the 5-HT 1A receptor [37].
• The selective 5-HT1A antagonist WAY-100635 reversed the effects of BAY in both areas, and the changes in the VTA were prevented by frontocortical transection [38].
• The highly selective 5-HT(1A) antagonist, WAY-100635, prevents the cognitive deficits induced not only by 5-HT(1A) stimulation but also by cholinergic or NMDA receptor blockade [22].
• In contrast, WAY 100635 (selective 5-HT1A antagonist) reversed the effect of 5-HT in hippocampus and entorhinal cortex [39].

Analytical, diagnostic and therapeutic context of Lopac-W-108

• Similar responses were obtained following local intra-raphe perfusion by reverse microdialysis of either WAY-100635 or (+/-)-pindolol (100 muM each) [15].
• In both nuclei this inhibitory effect was reversed by the selective 5-HT1A receptor antagonist, WAY 100635 (0.1 mg/kg i.v.). Microdialysis measurements were made in the frontal cortex and dorsal hippocampus, regions which receive a DRN- and an MRN-selective 5-HT innervation, respectively [40].
• Microinjection of a 5HT 1A antagonist (WAY 100635) into the spinal cord before intact rats received uncontrollable stimulation blocked the brain-dependent protection of spinal cord neurons [41].
• Positron emission tomography (PET) and [(11)C][O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635), were used to assess 5-HT(1A) autoreceptor and postsynaptic receptor occupancy in 12 healthy male volunteers [42].
• However, the intravenous injection of WAY 100635 (100 micrograms kg-1) readily suppressed the spontaneous firing activity of LC NA neurones [43].

References