Disease relevance of HS-592

• The ability of the H1 receptor antagonist clemastine to prevent exercise-induced asthma (EIA) has been studied in 10 adult asthmatic subjects [1].
• Dexamethasone, clemastine, and ranitidine were given for hypersensitivity prophylaxis [2].
• Randomized controlled trial of clemastine fumarate for treatment of experimental rhinovirus colds [3].
• Effectiveness of clemastine fumarate for treatment of rhinorrhea and sneezing associated with the common cold [4].
• One hundred and seven hay fever patients, sensitive to birch pollen, were randomized into three parallel groups receiving loratadine 40 mg once daily, clemastine 1 mg twice daily, or placebo during the birch pollen season [5].

Psychiatry related information on HS-592

• The effects of a single 10 mg dose of the new H1 antihistamine mizolastine on psychomotor performance and memory in the elderly were assessed in a double-blind, cross-over, placebo-controlled study in 15 elderly female volunteers aged 66-77 years, using clemastine 2 mg as a positive control [6].
• Astemizole in the treatment of seasonal allergic rhinitis. A double- blind comparison with clemastine in patients sensitive to tree and grass pollen. Special reference to side effects registered in psychological tests [7].

High impact information on HS-592

• In contrast, histamine at a concentration of 10(-2) M had an inhibitory effect on cell proliferation which was accentuated by cimetidine and partially reversed by promethazine and clemastine [8].
• Drowsiness due to clemastine transmitted in breast milk [9].
• Dexamethasone, clemastine, and ranitidine were standard premedication before every cycle [10].
• Single doses of ketotifen (0.5 mg), clemastine (0.5 mg), sodium cromoglycate (20 mg), or placebo were administered by inhalation 45 minutes before bronchial provocation testing at weekly intervals, double blind and in random order [11].
• The effects on airflow resistance of an inhaled H1 receptor antagonist, clemastine, and an H2 receptor antagonist, cimetidine, have been investigated in normal and asthmatic subjects [12].

Chemical compound and disease context of HS-592

• Finally, clemastine and mepyramine differed from ketotifen in their activities in a model of anaphylactically-induced bronchospasm [13].
• Risk of developing life-threatening ventricular arrhythmia associated with tefenadine in comparison with over-the-counter antihistamines, ibuprofen and clemastine [14].
• Cimetidine inhibited the tachycardia and clemastine reduced bradyarrhythmia [15].
• Intravenous fluid supplementation with subsequent decline of creatinine, UVB treatment, clemastine, and topical use of emollients led to a relief of the uremic pruritus and the lymph nodes' size normalized within 8 weeks [16].
• A comparative study of clemastine ('Tavegil') and chlorpheniramine maleate in the treatment of hay fever [17].

Biological context of HS-592

• There was a significant 21.9% increase in specific airways conductance after inhalation of clemastine [18].
• In five of the ten patients aspirin-precipitated bronchoconstriction was also reduced or prevented after pretreatment with clemastine [19].
• Clemastine was significantly better than placebo for both PEFR and FEV1 [1].
• IHERG tails at -40 mV following depolarizing pulses to +20 mV were inhibited by clemastine with an IC50 value of 12 nM; this drug concentration also produced a marked inhibition of peak IHERG elicited during an AP voltage-clamp command [20].
• The S6 point mutations Y652A and F656A greatly attenuated the inhibitory effect of clemastine [20].

Anatomical context of HS-592

• In target binding assays, clemastine fumarate and cimetidine also decreased the target binding capacity of effector lymphocytes [21].
• 5. The effects of sodium cromoglycate (SCG), clemastine and ketotifen administered to the nasal mucosa 30 min before provocation with histamine and allergen were compared in a random order, double-blind, placebo controlled study [22].
• These results indicate that the inhibitory effects of both KF and CF on Fc gamma R- and/or CR-mediated neutrophil oxidative potential is attributable to effects on an enzymatic reaction after protein kinase C activation in the oxidative signal transduction pathway [23].
• Azelastine and clemastine (50 mg/kg intraduodenally) reduced gastric secretion in pylorus ligated rats [24].
• The antihistamine activity of the compound is similar to that of clemastine fumarate in the following assays: histamine-induced lethality and bronchospasm in guinea-pigs, plasma extravasation in rats, and contractile action in isolated guinea-pig ileum [25].

Associations of HS-592 with other chemical compounds

• Clemastine did not protect subjects against methacholine-induced bronchoconstriction, which suggests that its bronchodilator properties are not related to any anticholinergic action [18].
• Ten antihistamine drugs, diphenhydramine, orphenadrine, chlorpheniramine, diphenylpyraline, triprolidine, promethazine, homochlorcyclizine, cyproheptadine, cloperastine and clemastine, have been found to be extractable from human plasma samples using MonoTip C18 tips, inside which C18- bonded monolithic silica gel was fixed [26].
• Ebastine 10 mg also differed positively from clemastine in the EEG features of vigilance [27].
• Clemastine did not significantly modify performance when given alone, and the performance decrements induced by ethanol were not enhanced by clemastine premedication [28].
• Phenobarbital also reduced the half life of aminopyrine, but it was not affected by clemastine or placebo [29].

Gene context of HS-592

• The GH dose was reduced to 0.2 mg/kg/wk and treatment for psoriasis (including hydrocortisone and clemastine) was started [30].
• This study investigated the effects on HERG channel current (IHERG) of clemastine, a "conventional" antihistamine that has been associated with delayed ventricular repolarization in vitro, but for which no adverse effects on the human QT interval have been reported [20].
• A multicentre study of loratadine, clemastine and placebo in patients with perennial allergic rhinitis [31].
• Group 3 animals received the histamine H1- and H2-antagonists clemastine and ranitidine 5 min before protamine infusion [32].
• The cyclooxygenase inhibitor indomethacin, the antihistamine clemastine, and the anti-oxidant superoxide dismutase also proved to be effective in the reduction of the dermatitis [33].

Analytical, diagnostic and therapeutic context of HS-592

• Identification of some new clemastine metabolites in dog, horse, and human urine with liquid chromatography/tandem mass spectrometry [34].
• Identification of urinary metabolites of clemastine after oral administration to man [35].
• The effects of single oral doses of 10 and 20 mg ebastine were compared with placebo and 2 mg clemastine in a double-blind cross-over study in 16 healthy male volunteers [27].
• No changes were observed after treatment with clemastine or placebo [29].
• The results showed that a single intramuscular injection of 2 mg clemastine was 'fully effective' in relieving the sumptoms of 19 (46.3%) patients, and gave 'some relief' in 20 (48.8%) [36].

References