Disease relevance of 2-Detpq

• Ten selected patients documented their migraine attacks over a 2-month period of open treatment with ICI 169,369, 30 mg orally, for acute therapy [1].
• ICI 169,369 did not significantly alter either ischaemia- or reperfusion-induced arrhythmias [2].
• However, all the antagonists except ICI 169,369 and methiothepin caused an increase in femoral arterial conductance which was not associated with hypotension [3].

High impact information on 2-Detpq

• The systemic administration of ICI 169,369 to portal hypertensive rats decreased portal pressure from 13.0 +/- 0.4 to 11.3 +/- 0.5 mmHg (p less than 0.01) but did not affect arterial pressure [4].
• The contractile effects of 5-hydroxytryptamine on isolated portal veins and superior mesenteric veins of portal hypertensive rats (portal vein constricted) were antagonized competitively by ICI 169,369 [4].
• Four non-selective 5-HT2C/5-HT2A receptor antagonists, mianserin (2-8 mg/kg), 1-naphthyl piperazine (1-NP) (0.5-1 mg/kg), ICI 169,369 (20 mg/kg) and LY 53857 (5 mg/kg), increased punished responding for a food reward in the rat Geller-Seifter test 30 min after subcutaneous (SC) administration [5].
• 7. The potency of RP 62203 was compared with that of three other 5-HT2 receptor antagonists, ritanserin, ICI 169,369 and ICI 170,809 [6].
• The 5-HT2 receptor antagonist ICI 169,369, even at high doses (up to 33 mumol/kg, s.c.), did not antagonize the rotational behavior induced by (+)-SKF 10,047.(ABSTRACT TRUNCATED AT 250 WORDS)[7]

Chemical compound and disease context of 2-Detpq

• Serotonin S2 receptors and migraine: a study with the selective antagonist ICI 169,369 [1].

Biological context of 2-Detpq

• ICI 169,369 and methysergide also compete for an allosteric site of the 5-HT2 receptor system, thereby facilitating the highly active R-state and low active R'-state, respectively [8].
• Cinanserin and ICI 169,369 did cause large transient changes in heart rate, blood pressure and sympathetic outflow [3].
• Results showed that ICI 169,369 had good oral bioavailability, since in the fenfluramine test the oral and s.c. ID50 values were similar [9].
• Administration of ketanserin, ritanserin, methiothepin or ICI 170,809, but not ICI 169,369, abolished the ability of 5-HT to enhance platelet aggregation [2].
• None of the above pretreatments affected the long-term fall in blood pressure caused by ICI 169,369 [10].

Anatomical context of 2-Detpq

• The receptors of portal veins of sham-operated rats had the same affinity for ICI 169,369 as the receptors of portal hypertensive rats [4].
• High concentrations of both ICI 169,369 and ICI 170,809 caused reductions in the maximum driving frequency of isolated cardiac muscle but methiothepin had no significant effect [2].
• In isolated tissue preparations ICI 169,369 was shown to be a competitive antagonist of 5-HT on the rabbit aorta, pig coronary artery and rat caudal artery [11].
• 1. The direct effects of ICI 169,369 on vascular reactivity were investigated in rabbit aortic rings with and without endothelium [12].
• It is concluded that ICI 169,369 has a post-receptor action, possibly by directly affecting intracellular calcium levels in the endothelial cells [12].

Associations of 2-Detpq with other chemical compounds

• ICI 169,369 (2-(2-dimethylaminoethylthio-3-phenylquinoline hydrochloride) has been tested in vivo for its potency and selectivity as an antagonist at 5-HT2 and 5-HT1C receptors [9].
• 3. Pretreatment with atropine methonitrate (1 mg kg-1) alone or in combination with atenolol (1 mg kg-1) or bi-vagotomy blocked the transient changes in blood pressure and heart rate caused by ICI 169,369 [10].
• 5. In pithed rats whose blood pressure was maintained with vasopressin, ICI 169,369 failed to cause any of the above transient and long-term effects on blood pressure and heart rate [10].

Gene context of 2-Detpq

• Since ICI 169,369 and ICI 170,809 are devoid of activity at 5-HT3 and 5-HT4 receptors, then these two subtypes would not appear to be implicated, a view that was confirmed in the case of 5-HT3 receptors by experiments using ondansetron.(ABSTRACT TRUNCATED AT 250 WORDS)[13]
• Evidence suggesting that the 5-HT2 antagonist ICI 169,369 activates vagal afferents and in addition has a central hypotensive action in anaesthetized rats [10].
• The effects of a 5-HT2 receptor antagonist (ICI 169,369) on changes in waking EEG, pupillary responses and state of arousal in human volunteers [14].
• MPD was reduced by 50% with the 120 mg dose at 5 h after dosing (placebo 5.2 mm; ICI 169,369 2.7 mm; P less than 0.05) [14].
• 3. Both doses of ICI 169,369 produced a mean 36% (range 10-54%) decrease in log 10 power of the waking EEG alpha activity with eyes closed (P less than 0.02), and mean 38% (range 2-86%) increase in theta activity at 2 h compared with placebo [14].

Analytical, diagnostic and therapeutic context of 2-Detpq

• ICI 169,369 induced nonsignificant changes in both portal venous inflow and portocollateral resistance, as estimated by the radioactive microsphere technique [4].
• Effects of ICI 169,369 as single oral doses (80 and 120 mg) separated by 1 week, on the power spectrum of waking EEG, dark adapted pupil responses and sedation score, were studied in a double-blind, placebo controlled, randomised cross over within subject comparison, in six healthy male volunteers [14].
• DESIGN: A double-blind, within-subject trial using a crossover design to compare the effect of placebo with two doses of ICI 169,369 on pituitary hormone responses to insulin-induced hypoglycaemia [15].
• After an initial ergotamine challenge to select responders to ergotamine, 10 selected volunteers were given in a double blind study an oral dose of either placebo, 30 mg or 120 mg of ICI 169,369 [16].
• From 6 to 8 hr after the administration, ergotamine caused a mean decrease in the toe-arm systolic gradient, measured by strain-gauge plethysmography of 32 mmHg (P < 0.001), which was not influenced by either 30 mg or 120 mg ICI 169,369 (P < 0.4) [16].

References