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Edward D. Levin - One of the best experts on this subject based on the ideXlab platform.

  • PPI deficit induced by amphetamine is attenuated by the Histamine H_1 Antagonist pyrilamine, but is exacerbated by the serotonin 5-HT_2 Antagonist ketanserin
    Psychopharmacology, 2010
    Co-Authors: José A. Larrauri, Edward D. Levin
    Abstract:

    Rationale Prepulse inhibition (PPI) of the startle response is a classic model of sensorimotor gating. Robust PPI impairments can be induced by dopamine agonists such as the indirect agonist amphetamine. The antipsychotic clozapine can attenuate PPI impairment induced by dopamine agonists. Clozapine is a complex drug with Antagonistic effects on a variety of receptors, including serotonin and Histamine. The relative contribution of its component actions to its efficacy is still unclear. Objectives To better characterize the role of Histamine and serotonin receptors in the modulation of PPI in rats, we studied the effects of the H_1 Histamine Antagonist pyrilamine (10, 20, and 40 mg/kg) on amphetamine-induced (1 mg/kg) PPI deficits (Experiment 1); and the interaction of pyrilamine (20 mg/kg) with the 5-HT_2 Antagonist ketanserin (1 and 2 mg/kg) on the amphetamine-induced PPI disruption (Experiment 2). Methods Tactile startle stimuli consisted of 30 PSI air-puffs. Three acoustic prepulse intensity levels were used: 68, 71, and 77 dB, presented on a 65-dB background noise. In both experiments, all animals received all drug doses and combinations with different counterbalanced orders. Results Pyrilamine (20 mg/kg) was effective in counteracting the PPI impairment caused by amphetamine administration, whereas ketanserin exacerbated the amphetamine-induced PPI deficit. Conclusions Based on its ability to reverse amphetamine-induced PPI deficits, blockade of Histamine H_1 receptors seems to contribute to the therapeutic effect of the antipsychotic clozapine. Serotonin 5-HT_2-receptor blockade, though, does not appear to contribute to this effect, and may in fact detract from it.

  • PPI deficit induced by amphetamine is attenuated by the Histamine H1 Antagonist pyrilamine, but is exacerbated by the serotonin 5-HT2 Antagonist ketanserin
    Psychopharmacology, 2010
    Co-Authors: José A. Larrauri, Edward D. Levin
    Abstract:

    Prepulse inhibition (PPI) of the startle response is a classic model of sensorimotor gating. Robust PPI impairments can be induced by dopamine agonists such as the indirect agonist amphetamine. The antipsychotic clozapine can attenuate PPI impairment induced by dopamine agonists. Clozapine is a complex drug with Antagonistic effects on a variety of receptors, including serotonin and Histamine. The relative contribution of its component actions to its efficacy is still unclear. To better characterize the role of Histamine and serotonin receptors in the modulation of PPI in rats, we studied the effects of the H1 Histamine Antagonist pyrilamine (10, 20, and 40 mg/kg) on amphetamine-induced (1 mg/kg) PPI deficits (Experiment 1); and the interaction of pyrilamine (20 mg/kg) with the 5-HT2 Antagonist ketanserin (1 and 2 mg/kg) on the amphetamine-induced PPI disruption (Experiment 2). Tactile startle stimuli consisted of 30 PSI air-puffs. Three acoustic prepulse intensity levels were used: 68, 71, and 77 dB, presented on a 65-dB background noise. In both experiments, all animals received all drug doses and combinations with different counterbalanced orders. Pyrilamine (20 mg/kg) was effective in counteracting the PPI impairment caused by amphetamine administration, whereas ketanserin exacerbated the amphetamine-induced PPI deficit. Based on its ability to reverse amphetamine-induced PPI deficits, blockade of Histamine H1 receptors seems to contribute to the therapeutic effect of the antipsychotic clozapine. Serotonin 5-HT2-receptor blockade, though, does not appear to contribute to this effect, and may in fact detract from it.

Johannes Forster - One of the best experts on this subject based on the ideXlab platform.

  • Are topical corticosteroids superior to systemic Histamine Antagonists in treatment of allergic seasonal rhinitis
    Archives of disease in childhood, 2002
    Co-Authors: Charles Christoph Roehr, Johannes Forster
    Abstract:

    You receive a call from one of your adolescent patients, a 16 year old boy with a longstanding history of seasonal allergic rhinitis (SAR). He is currently treating his mainly nasal symptoms with an oral Histamine Antagonist (OH1A). His symptoms are getting increasingly difficult to control. He is worried about the upcoming hay fever season and asks for other treatment options. In a 16 year old [patient] are topical corticosteroids [intervention] more effective than oral Histamine Antagonists [comparison intervention] in the alleviation of symptoms of seasonal allergic rhinitis [outcome]? Search engine—PubMed: “allergic rhinitis and adrenal-cortex-hormones and meta-analysis” (MeSH-Terms). Search results—two articles found, one original meta-analysis. Secondary sources—Consensus Statement, European Academy of Allergology and Clinical Immunology. See table 1. View this table: Table 1 Topical corticosteroids v systemic Histamine Antagonists in treatment of allergic seasonal rhinitis The meta-analysis by Weiner et al …

Richard I. Shader - One of the best experts on this subject based on the ideXlab platform.

  • In vitro prediction of the terfenadine-ketoconazole pharmacokinetic interaction.
    Journal of clinical pharmacology, 1994
    Co-Authors: Lisa L. Von Moltke, David J. Greenblatt, Su Xiang Duan, Jerold S. Harmatz, Richard I. Shader
    Abstract:

    Biotransformation of the peripherally acting H-1 Histamine Antagonist, terfenadine, to its desalkyl and hydroxy metabolites was studied in vitro using microsomal preparations from six separate human livers. These metabolic reactions are mediated by the specific cytochrome P450-3A4. Addition of ketoconazole to the reaction mixtures reduced the rate of formation of both metabolites in a manner consistent with competitive inhibition. Ketoconazole inhibition constants (Ki) averaged 0.024 μM for the desalkyl terfenadine pathway, and 0.237 μM for the hydroxy terfenadine pathway. A mathematical model, based on the in vitro Ki values and the usual clinical range of plasma ketoconazole concentrations (1–5 μg/mL; 1.88 − 0.94 μM), predicted that plasma terfenadine levels during coadministration of ketoconazole would increase by a factor ranging from 13-fold to 59-fold relative to the same dose of terfenadine given without ketoconazole. Actual plasma terfenadine levels during terfenadine-ketoconazole coadministration in a clinical pharmacokinetic study were close to those predicted by the model. These plasma levels were associated with prolongation of the corrected QT interval, thereby explaining the potentially life-threatening ventricular arrhythmias reportedly associated with terfenadine-ketoconazole cotherapy. Thus, data from studies of drug metabolism in vitro can be used to predict and thereby possibly avoid clinically important drug interactions.

José A. Larrauri - One of the best experts on this subject based on the ideXlab platform.

  • PPI deficit induced by amphetamine is attenuated by the Histamine H_1 Antagonist pyrilamine, but is exacerbated by the serotonin 5-HT_2 Antagonist ketanserin
    Psychopharmacology, 2010
    Co-Authors: José A. Larrauri, Edward D. Levin
    Abstract:

    Rationale Prepulse inhibition (PPI) of the startle response is a classic model of sensorimotor gating. Robust PPI impairments can be induced by dopamine agonists such as the indirect agonist amphetamine. The antipsychotic clozapine can attenuate PPI impairment induced by dopamine agonists. Clozapine is a complex drug with Antagonistic effects on a variety of receptors, including serotonin and Histamine. The relative contribution of its component actions to its efficacy is still unclear. Objectives To better characterize the role of Histamine and serotonin receptors in the modulation of PPI in rats, we studied the effects of the H_1 Histamine Antagonist pyrilamine (10, 20, and 40 mg/kg) on amphetamine-induced (1 mg/kg) PPI deficits (Experiment 1); and the interaction of pyrilamine (20 mg/kg) with the 5-HT_2 Antagonist ketanserin (1 and 2 mg/kg) on the amphetamine-induced PPI disruption (Experiment 2). Methods Tactile startle stimuli consisted of 30 PSI air-puffs. Three acoustic prepulse intensity levels were used: 68, 71, and 77 dB, presented on a 65-dB background noise. In both experiments, all animals received all drug doses and combinations with different counterbalanced orders. Results Pyrilamine (20 mg/kg) was effective in counteracting the PPI impairment caused by amphetamine administration, whereas ketanserin exacerbated the amphetamine-induced PPI deficit. Conclusions Based on its ability to reverse amphetamine-induced PPI deficits, blockade of Histamine H_1 receptors seems to contribute to the therapeutic effect of the antipsychotic clozapine. Serotonin 5-HT_2-receptor blockade, though, does not appear to contribute to this effect, and may in fact detract from it.

  • PPI deficit induced by amphetamine is attenuated by the Histamine H1 Antagonist pyrilamine, but is exacerbated by the serotonin 5-HT2 Antagonist ketanserin
    Psychopharmacology, 2010
    Co-Authors: José A. Larrauri, Edward D. Levin
    Abstract:

    Prepulse inhibition (PPI) of the startle response is a classic model of sensorimotor gating. Robust PPI impairments can be induced by dopamine agonists such as the indirect agonist amphetamine. The antipsychotic clozapine can attenuate PPI impairment induced by dopamine agonists. Clozapine is a complex drug with Antagonistic effects on a variety of receptors, including serotonin and Histamine. The relative contribution of its component actions to its efficacy is still unclear. To better characterize the role of Histamine and serotonin receptors in the modulation of PPI in rats, we studied the effects of the H1 Histamine Antagonist pyrilamine (10, 20, and 40 mg/kg) on amphetamine-induced (1 mg/kg) PPI deficits (Experiment 1); and the interaction of pyrilamine (20 mg/kg) with the 5-HT2 Antagonist ketanserin (1 and 2 mg/kg) on the amphetamine-induced PPI disruption (Experiment 2). Tactile startle stimuli consisted of 30 PSI air-puffs. Three acoustic prepulse intensity levels were used: 68, 71, and 77 dB, presented on a 65-dB background noise. In both experiments, all animals received all drug doses and combinations with different counterbalanced orders. Pyrilamine (20 mg/kg) was effective in counteracting the PPI impairment caused by amphetamine administration, whereas ketanserin exacerbated the amphetamine-induced PPI deficit. Based on its ability to reverse amphetamine-induced PPI deficits, blockade of Histamine H1 receptors seems to contribute to the therapeutic effect of the antipsychotic clozapine. Serotonin 5-HT2-receptor blockade, though, does not appear to contribute to this effect, and may in fact detract from it.

J.‐c. Schwartz - One of the best experts on this subject based on the ideXlab platform.

  • Design of Potent Non-Thiourea H3-Receptor Histamine Antagonists
    Journal of medicinal chemistry, 1995
    Co-Authors: Charon Robin Ganellin, Monique Garbarg, J. M. Arrang, Xavier Ligneau, S. K. Hosseini, Y. S. Khalaf, W. Tertiuk, J.‐c. Schwartz
    Abstract:

    Starting from thioperamide, the first potent and selective H 3 -receptor Histamine Antagonist, analogues have been synthesized and tested in vitro on rat cerebral cortex to explore structure-activity relationships. The aim has been to design potent compounds which do not possess the thiourea group of thioperamide and which may have improved brain penetration. In a short series of open chain thiourea analogues, the optimum chain length for H 3 -Antagonist potency was found to be (CH 2 ) 3 . Compounds derived from Histamine and possessing an aromatic nitrogen-containing heterocycle on the side chain amino group in place of thiourea show H 3 -Antagonist activity. Furthermore, when the heterocycle is 2-pyridyl, electron-withdrawing substituents (e.g. NO 2 , CF 3 , CO 2 Me) in the pyridine 5-position increased potency. The synthesis of 4-[4(5)-imidazolyl]piperidine and its conversion into the (trifluoromethyl)pyridyl analogue 5b of thioperamide is described ; however, 5b is not as potent as thioperamide. Replacing imidazole by pyridine or substituting imidazole on the remote N considerably reduced potency. Replacing the side-chain NH by S increased potency still further and the most potent compound is 2-{[2-[4(5)-imidazolyl]ethyl]thio}-5-nitropyridine (UCL 1199) which has K i = 4.8 nM