Vasomotor effect of histamine on pig and cattle coronary artery in vitro.
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Vasomotor effects of histamine were examined in isolated coronary arteries from pigs and cattle. Histamine produced a concentration-dependent contraction in these arteries. These contractile responses were dose-dependently inhibited by diphenhydramine. The slopes of the Schild plots, however, were significantly lower than unity in both species. Cimetidine potentiated the histamine-induced contractions at relatively high doses of histamine (larger than 10(-5) M) in pig coronary arteries, but did not show a significant effect in cattle arteries. After the removal of endothelium, the Schild plot of diphenhydramine against histamine gave a straight line with a pA2 value of 7.80 and slope of 1.00 in pigs, confirming the competitive nature of the antagonism. In cattle, the slope was significantly lower than unity; however, in the presence of cimetidine, it was not significantly different from unity. Dimaprit did not contract the cattle coronary arteries with endothelium, but contracted them after the removal of endothelium. These results suggest that histamine-induced vasoconstriction in pig and cattle coronary arteries is mainly dependent on the H1-receptors in the smooth muscle cells, and that H1- and H2-receptors in the endothelial cells of pigs and H2-receptors in the smooth muscle cells of cattle modify the histamine-induced vasoconstrictions. (+info)
Systemic vs. central administration of common hypnotics reveals opposing effects on genioglossus muscle activity in rats.
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STUDY OBJECTIVES: To determine if systemic administration of selected sedative-hypnotics that modulate the function of the y-amino-butyric acid-A (GABAA) receptor can: (i) delay arousal thereby allowing genioglossus (GG) activity to increase more in response to respiratory stimulation during sleep, (ii) also cause the robust increase in GG activity during undisturbed sleep recently observed with barbiturates. We also determined effects on GG activity with local application to the hypoglossal motor nucleus (HMN). DESIGN, PARTICIPANTS, AND INTERVENTIONS: Sleep-wake states, GG and diaphragm activities were recorded in freely-behaving rats after systemic administration of lorazepam (0.5 mg/kg and 1 mg/kg, n = 9 and 5 mg/kg, n = 7), zolpidem (5 mg/kg and 10 mg/kg, n = 6) and the antihistamine diphenhydramine (20 mg/kg, n = 9). Rats were also exposed to ramp increases in inspired CO2 in NREM sleep. The effects of lorazepam and zolpidem applied directly to the HMN were also determined in 37 anesthetized rats. MEASUREMENTS AND RESULTS: Lorazepam, zolpidem and diphenhydramine all increased arousal threshold, consistent with their sedative action. GG activity before arousal in response to hypercapnia was increased with lorazepam and zolpidem only, an effect mainly due to increased baseline activity before CO2 stimulation. Lorazepam and zolpidem applied directly to the HMN, however, decreased GG activity. CONCLUSIONS: Lorazepam and zolpidem have an inhibitory effect on GG activity via local effects at the HMN. Following systemic administration, however, this inhibitory effect can be outweighed both by a delay in arousal (allowing greater CO2-mediated respiratory stimulation in sleep) and excitatory influences on baseline GG activity via mechanisms operating outside the HMN. (+info)
Selective determination of diphenhydramine in compound pharmaceutical containing ephedrine by flow-injection electrochemiluminescence.
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On the basis of the structural interactions between diphenhydramine (DPH) and ephedrine (EPH) to enhance electrochemiluminescence (ECL) intensity, a flow-injection ECL analysis of DPH in the present of EPH by utilizing tris(2,2'-bipyridine)ruthenium(II), (Ru(bpy)(3)2+) has been reported. In the optimized experimental conditions, the linear ECL response to concentrations of DPH is from 2.00 to 40.0 microg/L with a correlation coefficient of 0.9995 and a detection limit of 1.20 microg/L. The relative standard deviation (RSD) was less than 4.6% (n=5) and the recovery was in the range of 98-106% for the determination of DPH in pharmaceutical samples. The method avoids any interference of coexistent EPH in the compounding drug without prior separation. The method has advantages over HPLC method in terms of speed and convenience, economics and safe procedure, and could be an alternative for places where HPLC equipment is not available. (+info)
Brain histamine H1 receptor occupancy of orally administered antihistamines, bepotastine and diphenhydramine, measured by PET with 11C-doxepin.
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Pharmacological screening of Ageratum conyzoides L. (Mentrasto).
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The pharmacological activities of a water extract (WE) of Ageratum conyzoides L, a plant popularly known for its analgesic and anti-inflammatory properties, were studied in vivo and in vitro preparations. Oral administration (p.o.) of the water extract (WE, 0.1 to 5 g/kg) to rats and mice induced quietness and reduced the spontaneous motility. The sleeping time induced by sodium pentobarbital (50 mg/kg, i.p.) in mice was not altered by previous treatment with WE (2 g/kg, p.o.). The same treatment did not influence the paw edema induced by carrageenan or dextran, nor did it reduce the chronic paw edema induced by complete Freund's adjuvant or formaldehyde in rats. The tail flick response in immersion test and writhings induced by 0.8% acetic acid in mice were not altered by WE either. In isolated guinea-pig ilea WE (0.4 to 4 mg/ml) did not alter the EC50 values of histamine or acetylcholine, but reduced the maximal response to the agonists by 20 to 50%. WE (0.01 to 10 mg/ml) produced tonic contractions of the ileal smooth muscle proportional to the doses, reaching a maximum of 75% relatively to the maximum obtained with histamine. Those contractions were blocked by diphenhydramine (10 nM) and reduced by 32% in presence of atropine (10 nM). The results indicated that oral treatment of rodents with A. conyzoides L neither reduced the inflammatory edema nor did it decrease the reaction to pain stimuli. In vitro the extract presented an unexpected histamine-like activity characteristic of a partial agonist. The results did not confirm the popular medicinal indications of the plant. (+info)
Taste mask, design and evaluation of an oral formulation using ion exchange resin as drug carrier.
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Effect of a pharmaceutical cationic exchange resin on the properties of controlled release diphenhydramine hydrochloride matrices using Methocel K4M or Ethocel 7cP as matrix formers.
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Emedastine difumarate inhibits histamine-induced collagen synthesis in dermal fibroblasts.
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BACKGROUND: Mast cell-derived histamine is known to act on dermal fibroblasts and contribute to formation of an intractable chronic allergic dermatitis. Although this fibrotic event may also occur in other organs such as the nasal mucosa, no direct evidence has been reported as to whether responsiveness to histamine by fibroblasts derived from different organs is of the same intensity. Furthermore, while type 1 histamine receptor (H1R) blockers have been shown to be effective for alleviation of the symptoms of allergic diseases, their ability to affect histamine-induced tissue remodeling has not yet been clarified. OBJECTIVE: Our aim was to study the effect of H1R-blockers on histamine-induced tissue remodeling. METHODS: A macroarray assay was used for a comprehensive analysis of histamine-induced gene expression by normal human fibroblasts. Fibroblasts derived from skin or nasal mucosa were cultured in the presence of various concentrations of histamine, and the synthesis of type 1 collagen was measured by means of semi-quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. To determine the effect of H1R blockers, diphenhydramine hydrochloride and emedastine difumarate were investigated in this assay. RESULTS: Histamine induced expression of various kinds of fibrogenic molecules in fibroblasts. Increased type 1 collagen expression was observed in fibroblasts treated with high-dose (0.1 mM to 1 microM) and low-dose (1 pM) histamine. This histamine-induced type 1 collagen synthesis was effectively diminished by emedastine difumarate. While organ specificity seems to be involved, emedastine difumarate is considered to be an effective drug for reversal of such histamine-induced remodeling in the skin. CONCLUSIONS: We found that the expression of fibroblast-derived genes is differentially regulated by different concentrations of histamine and that the robustness of the inhibitory action of H1R blockers is different for skin-derived and nasal mucosa-derived fibroblasts. We believe that our findings may contribute to a better understanding of the mechanisms of histamine-induced tissue remodeling and provide information useful for the management of refractory allergic dermatitis. (+info)