Concomitant administration of an H1-receptor antagonist with an H2-receptor antagonist may enhance the wheal and flare suppression produced by the H1-antagonist.
In this study co-administration of hydroxyzine with cimetidine resulted in significantly increased serum hydroxyzine concentrations and increased wheal and flare suppression, thus confirming the rationale for a trial of concomitant administration of these medications in some patients with chronic urticaria unresponsive to treatment with an H1-antagonist alone.
The dissociation constant between diphenhydramine and the inactivated Na(+) channel is approximately 10 microM, whereas the dissociation constant between diphenhydramine and the resting channel is more than 300 microM.
The local anesthetic effect of diphenhydramine thus is ascribable to inhibition of Na(+) current by selective binding of the drug to the inactivated channels.
Allergic rhinitis is more appropriately managed with the relatively nonimpairing second-generation antihistamines (eg, loratadine, desloratadine, cetirizine, and fexofenadine), because older agents (eg, diphenhydramine, chlorpheniramine, and brompheniramine) produce sedation and impairment and worsen sleep architecture.
This suggests that the promethazine-sensitive binding of [(3)H]-mepyramine includes a lower affinity non-receptor component, which becomes apparent at higher concentrations of [(3)H]-mepyramine.3 In the guinea-pig the dissociation constant for mepyramine determined from inhibition of [(3)H]-mepyramine binding was in good agreement with the value obtained from inhibition of the contractile response of intestinal smooth muscle to histamine.
Rat ileum was much less sensitive to histamine and the contraction produced was not inhibited by 10(-6) M mepyramine, indicating that it is not mediated by H(1)-receptors.4 Low levels of promethazine-sensitive [(3)H]-mepyramine binding were present in membrane fractions prepared from the longitudinal muscle from rat small intestine, but the characteristics of this binding suggest that it may be largely to lower affinity, non-receptor sites.5 Promethazine was practically equipotent as an inhibitor of [(3)H]-mepyramine binding in rat and guinea-pig brain.
1 The equilibrium dissociation constant, K(d), for mepyramine binding to a particulate fraction from rat brain, 9.1 nM, determined from inhibition of the binding of 1 nM [(3)H]-mepyramine, was distinctly higher than that, 0.83 nM, measured on an equivalent preparation from guinea-pig brain.2 In rat brain the dissociation constant for mepyramine, determined from the binding of [(3)H]-mepyramine sensitive to inhibition by 2 x 10(-6) M promethazine, was higher than the constant obtained from the inhibition of the binding of 1 nM [(3)H]-mepyramine by non-radioactive mepyramine.
The pharmacologic effects of hydroxyzine and cetirizine were monitored by measuring the suppression of histamine-induced wheals, using an IBM-PC and digitizer.
Terfenadine blockade of I(Na) was characterized by an important tonic block that accounted for approximately 50% of the total block.
Terfenadineblocks I(Na) in both rested state and inactivated state of the channels, but preferentially interacts with the former.
The effects of terfenadine on I(Na) were voltage dependent, as indicated with greater inhibition at less-negative holding potentials and at more-positive test potentials.
In mice, desloratadine exhibits an ED50 of 0.15 mg/kg in reduction of histamine induced paw edema .
Administration of desloratadine (1.0 mg/kg) significantly inhibited oxotremorine-induced (0.00125, 0.0025, and 0.02 mg/kg) decreases in dP/dt indicated by a shift in the dose-response curve to the right.
Inhibition of oxotremorine-induced alterations in cardiac function before and after either desloratadine, methoctramine, or 4-DAMP administration was analyzed via the paired t-test with changes in cardiac function at each dose of oxotremorine being compared.
In contrast, following treatment with the vasopressor agent, phenylephrine, to open the blood-brain barrier, a previously ineffective dose of desloratadine (1.0 mg/kg) caused a 60% reduction in tremor severity.
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Molecular Biology Examples
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cell cycle - looking for information
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