Influences of dimethindene maleate in a new formulation on oculo and psychomotor performance using the oculodynamic test (ODT) in volunteers

Schaffler, K.; Wauschkuhn, C H; Filho, Martino Martinelli; Rehn, D; Brunnauer, H.

doi:10.1007/bf02007800

Cited by 6 publications

(2 citation statements)

References 2 publications

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“…No adverse events like tiredness or dizziness were reported by any of the subjects during the study. This is consistent with other "sedative antihistamines" when used in low doses, "slow-onset" paradigms, in retarded formulations or given in multiple doses [37,40]. In studies on back pain [7,16,28] a block of mono-or polysynaptic reflexes by orphenadrine citrate or other relevant side effects were not observed.…”

Section: Discussionsupporting

confidence: 83%

Analgesic Effects of Low-dose Intravenous Orphenadrine in the State of Capsaicin Hyperalgesia

Schaffler

Reitmeir²

2011

Arzneimittelforschung

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The present investigation aimed to elucidate the analgesic efficacy of 30 mg of intravenous orphenadrine citrate (CAS 4682-36-4) in a human pain model. Eighteen healthy female and male subjects were enrolled and received single infusions of 30 mg orphenadrine citrate and matching placebo in two periods which were separated by a 1 week washout period. The study was designed as a randomised, double-blind, placebo-controlled, two-period, cross-over trial. The intended neurogenic inflammation and hyperalgesia were induced by topical, occlusive application of 1% capsaicin solution (INCI: Capsicum frutescens, containing capsaicinoides from Capsicum annuum annuum, CAS 84603-55-4) for 30 min on defined skin areas of the back. The pain response to CO2 laser pulses applied to the capsaicin pre-treated skin was measured by event related Vertex-EEG recordings. This technique allowed studying the influence of orphenadrine citrate on the (central) P2-component and the (peripheral) Ni-component of the pain response (LSEP). Both, orphenadrine citrate and placebo were given as intravenous infusions over 60 min. Orphenadrine citrate exerted a significant reduction in central and peripheral components of the pain response when compared to placebo. The effect on the central component was highly significant and more pronounced than the peripheral effect of the drug. The analgesic effect developed fast, was already present during infusion, was ongoing, and exceeded the observational period of 4 h after start of infusion. In summary, orphenadrine citrate was able to exert an analgesic/anti-hyperalgesic effect in a low-dose paradigm (30 mg dose) which was predominantly due to central/spinal mechanisms in this capsaicin model with laser somatosensory evoked potentials.

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Section: Discussionsupporting

confidence: 83%

Analgesic Effects of Low-dose Intravenous Orphenadrine in the State of Capsaicin Hyperalgesia

Schaffler

Reitmeir²

2011

Arzneimittelforschung

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“…It is noted that the constructed model indicated non-sedative properties of dimetindene, although dimetindene is classified as a first-generation of antihistamine. In good accordance with this, there are evidences that dimetindene is as non-sedative as loratadine (23,24). Furthermore, the constructed model well predicted non-sedative properties of bilastine (25), a newly-developed antihistamine, with a predicted DAUC value of 45.7 arbitrary units.…”

Section: Multiple Regression Analysessupporting

confidence: 53%

Molecular Determinants Responsible for Sedative and Non-sedative Properties of Histamine H1–Receptor Antagonists

2014

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Abstract. There is argument whether non-sedative properties of histamine H 1 -receptor antagonists (antihistamines) are determined by their active extrusions from the brain via P-glycoprotein or their restricted penetration through the blood-brain barrier. We have reported that sedative and non-sedative antihistamines can be well discriminated by measuring changes in their binding to H 1 receptors upon receptor internalization in intact cells, which depends on their membranepenetrating ability. In this study, molecular determinants responsible for sedative and non-sedative properties of antihistamines were evaluated by quantitative structure-activity relationship (QSAR) analyses. Multiple regression analyses were applied to construct a QSAR model, taking internalization-mediated changes in the binding of antihistamines as objective variables and their structural descriptors as explanatory variables. The multiple regression model was successfully constructed with two explanatory variables, i.e., lipophilicity of the compounds at physiological pH (logD) and mean information content on the distance degree equality (IDDE) (r 2 = 0.753). The constructed model discriminated between sedative and non-sedative antihistamines with 94% accuracy for external validation. These results suggest that logD and IDDE concerning lipophilicity and molecular shapes of compounds, respectively, predominantly determine the membranepenetrating ability of antihistamines for their side effects on the central nervous system.

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Sedation and antihistamines: a review of inter-drug differences using proportional impairment ratios

Shamsi

Hindmarch

2000

Hum. Psychopharmacol. Clin. Exp.

105

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The use of antihistamines (AHs) has until recently been associated with a number of undesirable side effects, the most troublesome of which is sedation. There are two aspects to sedation. The first, an objectively determined measure based on the results of psychometric tests from controlled trials, and the second, the subject's response to the administration of a drug. Since AHs are largely used in ambulant patients, a complete evaluation of sedation should be performed through standardised objective and subjective tests, shown to be sensitive to the central effects of AHs. An extensive review of the literature identified 76 studies of H1 receptor antagonists in healthy volunteers, in which assessment of sedation was the primary objective. Results from studies published in peer‐reviewed journals which employed a placebo condition as well as a positive internal control using a crossover design were analysed to determine the extent to which a particular antihistamine produced impairments on a battery of psychometric tests. The impairment index for each antihistamine was calculated and subsequently compared with the impairment index obtained for all other AHs. The calculation of this proportional impairment ratio enabled the sedative potential of an individual antihistamine to be identified relative to all other AHs and thus allowed the ranking of AHs with respect to their ability to cause impairments of cognitive and psychomotor function. Findings from this review clearly demonstrate that there are distinct classes of AHs with respect to their ability to impair cognitive function and psychomotor performance. Copyright © 2000 John Wiley & Sons, Ltd.

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Influences of dimethindene maleate in a new formulation on oculo and psychomotor performance using the oculodynamic test (ODT) in volunteers

Cited by 6 publications

References 2 publications

Analgesic Effects of Low-dose Intravenous Orphenadrine in the State of Capsaicin Hyperalgesia

Analgesic Effects of Low-dose Intravenous Orphenadrine in the State of Capsaicin Hyperalgesia

Molecular Determinants Responsible for Sedative and Non-sedative Properties of Histamine H1–Receptor Antagonists

Sedation and antihistamines: a review of inter-drug differences using proportional impairment ratios

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