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Douglas J. Coster - One of the best experts on this subject based on the ideXlab platform.
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clinical evaluation of twice daily emedastine 0 05 eye drops emadine eye drops versus levocabastine 0 05 eye drops in patients with allergic conjunctivitis
American Journal of Ophthalmology, 2001Co-Authors: Ph Verin, D.l Easty, Antonio G. Secchi, G. Ciprandi, P Partouche, Rosario Brancato, C.j Harrisberg, G Nemethwasmer, C Estivinebrardt, Douglas J. CosterAbstract:Abstract PURPOSE: The efficacy and safety of emedastine 0.05% eye drops (Emadine; Alcon Laboratories, Inc, Fort Worth, Texas), a new H1 Antagonist, were studied in comparison to levocabastine 0.05% eye drops (Livostin; Janssen-Cilag N V, Berchem, Belgium) during a twice-daily treatment schedule for 6 weeks in adult and pediatric patients with seasonal allergic conjunctivitis. METHODS: In a prospective, multicenter, randomized, double-masked, parallel group study, 222 patients with allergic conjunctivitis were randomized (221 received treatment) to either emedastine or levocabastine, instilled twice daily for 6 weeks. Patient diaries were completed four times daily (before the morning and evening instillations, at noon, and in the afternoon), and clinical examinations were conducted at regular intervals. Primary efficacy variables of ocular redness and itching and secondary efficacy variables of chemosis, eyelid swelling, patient diary data, and physician’s global assessment were analyzed. RESULTS: Both emedastine and levocabastine produced a statistically significant (P = .0001) reduction in itching and redness within 5 minutes of the first instillation. All signs and symptoms improved progressively over the 6-week treatment period. After 7 days of use, and throughout the remainder of the study, emedastine was statistically superior to levocabastine (P CONCLUSIONS: Emedastine 0.05% eye drops administered twice daily are more efficacious than levocabastine 0.05% eye drops in the prevention and treatment of the signs and symptoms of allergic conjunctivitis in adults and children of 4 years and above. Both emedastine 0.05% eye drops and levocabastine 0.05% eye drops were well tolerated.
Randall D Armant - One of the best experts on this subject based on the ideXlab platform.
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histamine enhances cytotrophoblast invasion by inducing intracellular calcium transients through the histamine type 1 receptor
Molecular Reproduction and Development, 2004Co-Authors: Zitao Liu, Brian A Kilburn, Richard E Leach, Roberto Romero, Bibhash C Paria, Randall D ArmantAbstract:Blastocyst implantation and pla- centation require molecular and cellular interactions between the uterine endometrium and blastocyst trophectoderm. Previous studies showed that hista- mine produced in the mouse uterine luminal epithe- lium interacts with trophoblast histamine type-2 receptors (H2) to initiate blastocyst implantation. However, it is unknown whether similar histamine activity is operative in humans. Using a human cell line (HTR-8/SVneo) derived from first-trimester cytotropho- blasts that expresses both histamine type-1 receptor (H1) and H2, we found that histamine promotes cyto- trophoblast invasiveness specifically through activation of H1. Stimulation of H1 in human cytotrophoblasts by histamine induced intracellular Ca 2þ (Ca 2þ i) transients by activating phospholipase C and the inositol trispho- sphate pathway. The enhanced invasion induced by histamine was blocked by pretreatment with H1 Antagonist or by chelation of Ca 2þ i. These findings suggest possible differences between rodents and humans in histamine signaling to the trophoblast. Mol. Reprod. Dev. 68: 345-353, 2004. 2004 Wiley-Liss, Inc.
Walter Schunack - One of the best experts on this subject based on the ideXlab platform.
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combined histamine H1 h2 receptor Antagonists part i pharmacological hybrids with pheniramine and roxatidine like substructures
European Journal of Pharmaceutical Sciences, 1998Co-Authors: Frank R Schulze, Armin Buschauer, Walter SchunackAbstract:A series of hybrid compounds combining the pharmacophores of both pheniramine-type histamine H1 receptor Antagonists and roxatidine-type H2 receptor Antagonists have been synthesized and tested for histamine antagonism at the isolated ileum (H1) and the spontaneously beating right atrium (H2) of the guinea pig. The 'polar group' of the H2 Antagonist moiety (cyanoguanidine, nitroethenediamine or urea) and the side chain amino group of the H1 Antagonist portion have been linked by a polymethylene spacer or by a piperazine system. The incorporation of a flexible spacer (2-7 methylene groups) resulted in H1 Antagonists achieving up to 2.4 times the activity of pheniramine. Depending on the nature of the polar group the highest H2 Antagonist potency resides in compounds with spacers ?2 methylene groups. Nitroethenediamine 24c with a seven-membered chain and a chlorpheniramine substructure proved to be approximately equipotent with pheniramine at the H1 and with ranitidine at the H2 receptor (pKB values 7.82 and 7.1, respectively).
Roberto Romero - One of the best experts on this subject based on the ideXlab platform.
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histamine enhances cytotrophoblast invasion by inducing intracellular calcium transients through the histamine type 1 receptor
Molecular Reproduction and Development, 2004Co-Authors: Zitao Liu, Brian A Kilburn, Richard E Leach, Roberto Romero, Bibhash C Paria, Randall D ArmantAbstract:Blastocyst implantation and pla- centation require molecular and cellular interactions between the uterine endometrium and blastocyst trophectoderm. Previous studies showed that hista- mine produced in the mouse uterine luminal epithe- lium interacts with trophoblast histamine type-2 receptors (H2) to initiate blastocyst implantation. However, it is unknown whether similar histamine activity is operative in humans. Using a human cell line (HTR-8/SVneo) derived from first-trimester cytotropho- blasts that expresses both histamine type-1 receptor (H1) and H2, we found that histamine promotes cyto- trophoblast invasiveness specifically through activation of H1. Stimulation of H1 in human cytotrophoblasts by histamine induced intracellular Ca 2þ (Ca 2þ i) transients by activating phospholipase C and the inositol trispho- sphate pathway. The enhanced invasion induced by histamine was blocked by pretreatment with H1 Antagonist or by chelation of Ca 2þ i. These findings suggest possible differences between rodents and humans in histamine signaling to the trophoblast. Mol. Reprod. Dev. 68: 345-353, 2004. 2004 Wiley-Liss, Inc.
Robbie L Mcleod - One of the best experts on this subject based on the ideXlab platform.
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pharmacological characterization of the novel histamine h3 receptor Antagonist n 3 5 dichlorophenyl n 4 1h imidazol 4 ylmethyl phenyl methyl urea sch 79687
Journal of Pharmacology and Experimental Therapeutics, 2003Co-Authors: Robbie L Mcleod, Charlie A Rizzo, Matthew S Bryant, Garfield G Mingo, Yunsheng Hsieh, Kevin D. Mccormick, Robert G. Aslanian, Robert E. West, Walter A. Korfmacher, Loriann VartyAbstract:We present the pharmacological and pharmacokinetic profiles of a novel histamine H3 receptor Antagonist, N-(3,5-dichlorophenyl)-N′-[[4-(1H-imidazol-4-ylmethyl)phenyl]-methyl]-urea (SCH 79687). The H3-receptor binding Ki values for SCH 79687 were 1.9 and 13 nM in the rat and guinea pig (GP), respectively. The Ki values for SCH 79687 at histamine H1 and H2 receptors were greater than 1 μM. SCH 79687 showed a 41- and 82-fold binding selectivity for the H3 receptor over α2A-adrenoceptors and imidazoline I2, and >500-fold H3 selectivity compared with over 60 additional receptors. The pA2 value for SCH 79687 in the GP ileum electrical field-stimulated (EFS) contraction was 9.6 ± 0.3. Similar H3 Antagonist activity was observed in the EFS cryopreserved and fresh tissue isolated human saphenous vein (HSV) assays (pKb = 9.4 ± 0.3 and 10.1 ± 0.4). SCH 79687 (30 nM) did not block clonidine-induced inhibition of EFS-induced contractions in HSV. SCH 79687 (ED50 = 0.3 mg/kg i.v.) attenuated (R)-α-methylhistamine inhibition of sympathetic hypertensive responses in the GP. At the time of activity evaluation, the GP plasma SCH 79687 concentration was 25 ng/ml at the dose of 0.3 mg/kg i.v. In feline nasal studies, combined administration of SCH 79687 (3 mg/kg i.v.) and the H1-Antagonist loratadine (3 mg/kg i.v.), at individual doses that do not produce decongestion, inhibited the compound 48/80-induced congestion by 47%. The α-adrenergic agonist phenylpropanolamine (PPA; 1 mg/kg i.v.) also attenuated compound 48/80 nasal responses by 42%. Unlike the H3/H1 combination that did not affect blood pressure (BP), PPA (1 mg/kg i.v.) significantly increased BP compared with control animals by a maximum of 31 mm Hg. Orally, SCH 79687 (10 mg/kg) plus loratadine (10 mg/kg) also produced decongestion without effects on BP. In pharmacokinetic studies, oral dosing with SCH 79687 in the rat (10 mg/kg) and monkey (3 mg/kg) achieved plasma Cmax and area under the curve values greater than 1.5 and 12.1 μg · h/ml, respectively. SCH 79687 is an orally active H3 Antagonist with a good pharmacokinetic profile that, in combination with an H1 Antagonist, demonstrates decongestant efficacy comparable with oral sympathomimetic decongestants but without hypertensive liabilities.
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changes in nasal resistance and nasal geometry using pressure and acoustic rhinometry in a feline model of nasal congestion
American Journal of Rhinology, 1999Co-Authors: Robbie L Mcleod, Garfield G Mingo, Michel R Corboz, Christine Herczku, Sonia I Ramos, Frances Degennaroculver, O F Pedersen, John A. HeyAbstract:This is the first report describing the use and pharmacological characterization of nasal patency by both pressure rhinometry and acoustic rhinometry (AcR) in an experimental cat model of nasal congestion. In pressure rhinometry studies, aerosolized compound 48/80 (0.1-3.0%), a mast cell liberator, increased nasal airway resistance (NAR) 1.2 +/- 0.6, 5.8 +/- 0.5, 8.6 +/- 1.1 and 7.9 +/- 1.5 cmH2O.L/minute, respectively. Increases in NAR produced by compound 48/80 were associated with a 395% increase in histamine concentration found in the nasal lavage fluid. Pretreatment with the alpha-adrenoreceptor agonist, phenylpropanolamine (PPA; 0.1-3.0 mg/kg, i.v.), and the NO synthetase inhibitor, NG-nitro-L-arginine (L-NAME; 10 mg/kg, i.v.) attenuated the increases in NAR produced by compound 48/80. The histamine H1 Antagonist chlorpheniramine (1.0 mg/kg, i.v.) and the H2 Antagonist, ranitidine (1.0 mg/kg, i.v.) had no decongestant activity. Also without decongestant activity were the muscarinic Antagonist atropine, the cyclooxygenase inhibitor indomethacin, and the 5-HT blocker methysergide. Aerosolized histamine (0.1-1.0%) also produced a dose dependent increase in NAR. In studies using acoustic rhinometry (AcR), intranasal application of compound 48/80 (0.1-1.0%) elicited pronounced decreases in nasal cavity volumes and minimum cross-sectional area (Amin). Pretreatment with PPA (3 mg/kg, i.v. or 10 mg/kg, p.o.) attenuated the decreases in nasal volume and Amin. The effects of topical intranasal histamine (0.1-1.0%) on nasal geometry were similar to compound 48/80. We conclude that the cat is a useful model for evaluating the pharmacological actions of potential nasal decongestants. Furthermore, we also conclude that AcR is a useful method for noninvasive assessment of nasal patency in a preclinical setting.
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combined histamine H1 and h3 receptor blockade produces nasal decongestion in an experimental model of nasal congestion
American Journal of Rhinology, 1999Co-Authors: Robbie L Mcleod, Garfield G Mingo, Christine Herczku, Frances Degennaroculver, William Kreutner, Robert W Egan, John A. HeyAbstract:We studied the pharmacological actions of combined histamine H1/H3 receptor blockade on the increase in nasal airway resistance (NAR) and decrease in nasal cavity volume produced by nasal exposure to compound 48/80, a mast cell degranulator. In the anesthetized cat compound 48/80 (1%) produced a maximum increase in NAR of 9.1 +/- 0.7 cmH20.L/minute. The increase in NAR in animals pretreated with a combination of the H1 Antagonist, chlorpheniramine (CTM; 0.8 mg/kg i.v.) and increasing doses of the H3 Antagonist, thioperamide (THIO; 1.0, 3.0, and 10.0 mg/kg i.v.) were 6.1 +/- 2.1, 4.2 +/- 1.0 and 2.2 +/- 0.7 cmH20.L/minute, respectively. A second H3 Antagonist, clobenpropit (CLOB; 0.03, 0.3, and 1.0 mg/kg i.v.) combined with CTM (0.8 mg/kg i.v.) also inhibited the nasal effects of compound 48/80. When the nonsedating H1 antihistamine, loratadine (3.0 mg/kg i.v.), was substituted for CTM, it also reduced nasal congestion when given in combination with THIO (10 mg/kg i.v.). In contrast, treatment with CTM (1.0 mg/kg i.v.) and the H2 Antagonist, ranitidine (RAN; 1.0 mg/kg i.v.) were without activity. Loratadine, CTM, CLOB, RAN, or THIO administered alone were inactive. The alpha-adrenergic agonist, phenylpropanolamine (PPA; 1.0 mg/kg i.v.) demonstrated decongestant effects, but in contrast to H1/H3 blockade, PPA produced a significant hypertensive effect. Using acoustic rhinometry (AcR) we found that combined i.v. CTM (1.0 mg/kg) and THIO (10 mg/kg) and combined oral CTM (10 mg/kg) and THIO (30 mg/kg) blocked the decrease in nasal cavity volume produced by intranasal compound 48/80 (1%, 50 microL). We conclude that combined H1/H3 histamine receptor blockade enhances the efficacy of an H1 Antagonist by conferring decongestant activity to the H1 antihistamine. We propose that the decongestant activity of combined H1/H3 blockade may provide a novel approach for the treatment of allergic nasal congestion without the hypertensive liability of current therapies.