Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Topical application of the nonimmune selective mast-cell degranulating agent, compound 48/80, produced the signs and symptoms of ocular allergy (itching, injection, chemosis, and mucous discharge) in eight guinea pigs, eight rabbits, and nine humans. The histamine H1 receptor antagonist, antazoline phosphate, blocked itching but not vasodilation in five humans pretreated with compound 48-80. This suggests that histamine was one of the mediators released by compound 48-80-induced degranulation. Compound 48-80 may be helpful in evaluating the effects of therapeutic agents capable of modifying mast-cell degranulation and in the study of mediators involved in external ocular inflammation.
 ...
PMID:Animal and human ocular surface response to a topical nonimmune mast-cell degranulating agent (compound 48/80). 616 89

Ebastine is a new second generation histamine H1 receptor antagonist that has shown clinical efficacy in the treatment of seasonal and perennial allergic rhinitis and chronic urticaria after once-daily administration. This double-blind multicentre randomised placebo-controlled study has investigated the long term efficacy of ebastine 10mg once daily in the treatment of chronic urticaria compared with that of terfenadine 60mg twice daily. At the end of a 3-month treatment period, ebastine was significantly superior to placebo in improving symptoms of chronic urticaria (including severity of itching, number of wheals per day), and its efficacy was similar to that of terfenadine. In a global assessment of efficacy, investigators considered chronic urticaria to have improved in 73% of ebastine recipients compared with 68% and 52% of patients treated with terfenadine or placebo, respectively. The patients' assessments of efficacy were similar to those of the investigators. Ebastine was well tolerated, the incidence and nature of adverse events with this agent being similar to those reported in patients treated with terfenadine or placebo. The most common adverse events were headache and dry mouth. Thus, these results, which show ebastine to be an effective and well tolerated agent, indicated that the drug should be considered for the first-line therapy of chronic urticaria.
 ...
PMID:Double-blind multicentre comparative study of ebastine, terfenadine and placebo in the treatment of chronic idiopathic urticaria in adults. 882 24

Chlorpheniramine, a histamine H1 receptor antagonist, reverse chloroquine resistance in Plasmodium falciparum in vitro. However, the clinical significance of this remains unclear. We have evaluated the efficacy of chloroquine and a chloroquine-chlorpheniramine combination in 112 consecutive children with acute symptomatic uncomplicated falciparum malaria. There was no significant difference in the parasite and fever clearance times in the 2 treatment groups. However, the proportion of patients in whom parasitaemia increased 24 h after commencement of treatment was significantly higher in the chloroquine group than in the chloroquine-chlorpheniramine group (28.5% vs. 8.3%, chi 2 = 6.61, P < 0.01). There was also a higher proportion of children with RII and RIII responses to treatment in the chloroquine than in the chloroquine-chlorpheniramine group but the difference was not statistically significant. The cure rate on day 14 was higher in the chloroquine-chlorpheniramine group than in the chloroquine group. Chloroquine and its combination with chlorpheniramine were well tolerated, the only prominent adverse effect being pruritus, with equal incidence in both groups. Chlorpheniramine reversed chloroquine resistance in vitro in a similar manner to verapamil in isolates of P. falciparum obtained from the patients. Failure of a response in vivo to chloroquine correlated with resistance in vitro in patients treated with this drug. In contrast, all but one patient with isolates which were chloroquine resistant in vitro were successfully treated with chloroquine-chlorpheniramine combination. These data suggest the enhanced efficacy of chloroquine-chlorpheniramine combination in treating acute uncomplicated P. falciparum infection in children from an endemic area of Nigeria.
 ...
PMID:Enhanced efficacy of chloroquine-chlorpheniramine combination in acute uncomplicated falciparum malaria in children. 950 91

In the face of growing chloroquine resistance of Plasmodium falciparum, efforts to prolong the clinical usefulness of the drug have partly concentrated on its combination with potential resistance-reversing compounds. However, clinical studies on such combinations have been limited. We have compared the efficacy of halofantrine, an arylaminoalcohol effective in chloroquine resistant malaria, and a combination of chloroquine plus chlorpheniramine, a histamine H1 receptor antagonist which reverses chloroquine resistance of P. falciparum in vitro and in vivo, in 100 children with acute symptomatic uncomplicated falciparum malaria in an area in Nigeria where the rate of chloroquine resistance is 35-45%. Both chloroquine plus chlorpheniramine and halofantrine produced similar parasite and fever clearance times and cure rates (96%). Both treatment regimens were relatively well tolerated. Pruritus was commoner in patients treated with chloroquine plus chlorpheniramine than in those treated with halofantrine. Intravascular haemolysis occurred in one patient, and abdominal pain with or without diarrhoea occurred in 4 patients, treated with halofantrine. In vitro, the chloroquine resistance of P. falciparum isolates obtained from the patients was reversed by verapamil. All patients with isolates which were chloroquine-resistant in vitro were cured by either therapy. These results indicate that chloroquine plus chlorpheniramine is as effective as halofantrine and is without overt deleterious effect in treating acute uncomplicated chloroquine-resistant falciparum malaria in children, and may be a clinically useful alternative for this purpose in Nigeria.
 ...
PMID:Comparative efficacy of chloroquine plus chlorpheniramine and halofantrine in acute uncomplicated falciparum malaria in Nigerian children. 985 Apr 4

Second-generation histamine H1 receptor antagonists (antihistamines) have been developed to reduce or eliminate the sedation and anticholinergic adverse effects that occur with older H1 receptor antagonists. This article evaluates second-generation antihistamines, including acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, ketotifen, loratadine, mizolastine and terfenadine, for significant features that affect choice. In addition to their primary mechanism of antagonising histamine at the H1 receptor, these agents may act on other mediators of the allergic reaction. However, the clinical significance of activity beyond that mediated by histamine H1 receptor antagonism has yet to be demonstrated. Most of the agents reviewed are metabolised by the liver to active metabolites that play a significant role in their effect. Conditions that result in accumulation of astemizole, ebastine and terfenadine may prolong the QT interval and result in torsade de pointes. The remaining agents reviewed do not appear to have this risk. For allergic rhinitis, all agents are effective and the choice should be based on other factors. For urticaria, cetirizine and mizolastine demonstrate superior suppression of wheal and flare at the dosages recommended by the manufacturer. For atopic dermatitis, as adjunctive therapy to reduce pruritus, cetirizine, ketotifen and loratadine demonstrate efficacy. Although current evidence does not suggest a primary role for these agents in the management of asthma, it does support their use for asthmatic patients when there is coexisting allergic rhinitis, dermatitis or urticaria.
 ...
PMID:Second-generation antihistamines: a comparative review. 1040 Apr 11

Most of the modern non-sedating H1 receptor antagonists (antihistamines) penetrate the brain poorly, allowing the use of doses large enough to counteract allergic processes in peripheral tissues without important central effects. The antihistamines reviewed here are acrivastine, astemizole, cetirizine, ebastine, fexofenadine, loratadine, mizolastine, and terfenadine. However, these drugs are not entirely free from central effects, and there are at least quantitative differences between them. Although psychomotor and sleep studies in healthy subjects in the laboratory may predict that an antihistamine does not cause drowsiness, the safety margin can be narrow enough to cause a central sedating effect during actual treatment. This might result from a patient's individual sensitivity, disease-induced sedation, or drug dosages that are for various reasons relatively or absolutely larger (patient's weight, poor response, reduced drug clearance, interactions). Mild to even moderate sedation is not necessarily a major nuisance, particularly if stimulants need be added to the regimen (e.g. in perennial rhinitis). Furthermore, patients can adjust doses themselves if needed. Sedating antihistamines are not needed for long-term itching, because glucocorticoids are indicated and more effective. It is wise to restrict or avoid using antihistamines (astemizole, terfenadine) that can cause cardiac dysrhythmias, because even severe cardiotoxicity can occur in certain pharmacokinetic drug-drug interactions. Histamine H1 receptor antagonists (antihistamines) are used in the treatment of allergic disorders. The therapeutic effects of most of the older antihistamines were associated with sedating effects on the central nervous system (CNS) and antimuscarinic effects causing dry mouth and blurred vision. Non-specific "quinidine-like" or local anaesthetic actions often led to cardiotoxicity in animals and man. Although such adverse effects varied from drug to drug, there was some degree of sedation with all old antihistamines. Non-sedating antihistamines have become available during the past 15 years. Some of them also have antiserotonin or other actions that oppose allergic inflammation, and they are not entirely free from sedative effects either. In small to moderate "clinical" concentrations they are competitive H1 receptor antagonists, although large concentrations of some of them exert non-competitive blockade. Daytime drowsiness and weakness are seldom really important, and they restrict patients' activities less than the old antihistamines. Some new antihistamines share with old antihistamines quinidine-like effects on the cardiac conducting tissues, and clinically significant interactions have raised the question of drug safety. This prodysrhythmic effect has also been briefly mentioned in comparisons of non-sedative H1 antihistamines.
 ...
PMID:Variations among non-sedating antihistamines: are there real differences? 1033 1

The effects of the kappa-opioid receptor agonist, TRK-820, (-)-17-(cyclopropylmethyl)-3, 14beta-dihydroxy-4, 5alpha-epoxy-6beta-[N-methyl-trans-3-(3-furyl) acrylamido] morphinan hydrochloride, on the itch sensation were compared with those of histamine H1 receptor antagonists, using the mouse pruritogen-induced scratching model. Peroral administration of TRK-820 reduced the numbers of substance P- or histamine-induced scratches dose dependently. No obvious suppression of the spontaneous locomotor activity was observed at the doses used for the experiments, indicating that the inhibition of scratches was not due to the effect on general behavior. Furthermore, the scratching inhibitory activity of TRK-820 was dose dependently antagonized by the specific kappa-opioid receptor antagonist, nor-binaltorphimine, suggesting that the inhibitory activity was mediated via kappa-opioid receptors. Histamine H1 receptor antagonists, chlorpheniramine and ketotifen, did not inhibit substance P-induced scratches, or did so only partially. Both antihistamines inhibited the histamine-induced scratches completely. These results suggest that TRK-820 has antipruritic activity which is mediated by kappa-opioid receptors, and is effective in both antihistamine-sensitive and -resistant pruritus.
 ...
PMID:Antipruritic activity of the kappa-opioid receptor agonist, TRK-820. 1182 Oct 35

Histamine release from mast cells is a primary mediator of rhinorrhea, nasal mucosal swelling, increased secretion, sneezing, pruritus and congestion that occur in allergic rhinitis. It is well known that histamine H(1) receptor antagonists inhibit the itch and rhinorhea, but do not block the allergic nasal congestion. A growing body of evidence shows that in addition to histamine H(1) receptors, activation of H(3) receptors may contribute to the procongestant nasal actions of histamine. Activation of the prejunctional histamine H(3) receptor modulates sympathetic control of nasal vascular tone and resistance. The present study was conducted to further characterize the role of histamine H(3) receptors on neurogenic sympathetic vascular contractile responses in isolated porcine nasal turbinate mucosa. We presently found that the histamine H(3) receptor agonist, (R)-alpha-methylhistamine (10-1000 nM), inhibited electrical field stimulation-induced sympathetic vasomotor contractions in a concentration-dependent fashion. Pretreatment with either of the selective histamine H(3) receptor antagonists, thioperamide and clobenpropit, blocked the sympathoinhibitory effect of (R)-alpha-methylhistamine in porcine turbinate mucosa. The effect of compound 48/80, an agent that elicits the release of endogenous histamine from mast cells on nasal sympathetic contractile responses, was also tested. The action of compound 48/80 to release mast cell-derived histamine in the nose mimics many of the nasal responses associated with allergic rhinitis, extravascular leakage and decreased nasal patency. We presently found that compound 48/80 also inhibited the electrical field stimulation-induced sympathetic response. Pretreatment with the H(3) receptor antagonist clobenpropit blocked the sympathoinhibitory action of compound 48/80 on sympathetic contractile responses in nasal mucosa. Taken together, these studies indicate that histamine H(3) receptors modulate vascular contractile responses by inhibition of noradrenaline release from sympathetic nerve terminals in nasal mucosa. It is further suggested that histamine H(3) receptors may play a role in the regulation of vascular tone and nasal patency in allergic nasal congestive disease.
 ...
PMID:Histamine H3 receptor activation inhibits neurogenic sympathetic vasoconstriction in porcine nasal mucosa. 1235 75

It has been reported that antihistamines do not fully modify symptoms of allergic conjunctivitis in clinical settings, suggesting that histamine is not the only contributor to symptom generation in the disease. However, in the majority of experimental allergic conjunctivitis models, antihistamines are very effective in the reduction of symptoms. In the present study, we used our recently developed guinea pig model of allergic conjunctivitis and evaluated whether involvement of histamine in the induction of symptoms of allergic conjunctivitis is altered by multiple antigen challenges. Guinea pigs were sensitized by intraperitoneal injection of Japanese cedar pollen extracts adsorbed on aluminum hydroxide gel, and then challenged by dropping a pollen suspension without the adjuvant on each eye once a week until the 15th challenge. The magnitude of the conjunctivitis intensity score (CIS), itch-associated scratching response and albumin leakage were found to increase with repeated challenges. At the 1st-3rd challenges, histamine H(1) receptor antagonist, mepyramine (10 mg/kg, p.o.), strongly reduced all these symptoms. However, symptoms at the 5th-15th challenges were not inhibited by mepyramine. On the other hand, a nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (10 mg/kg, i.v.), potently inhibited the increase of CIS and albumin leakage at the 15th challenge. In conclusion, histamine involvement in the induction of conjunctivitis symptoms in our model was diminished by multiple antigen challenges. The allergic conjunctivitis at the chronic stage is partly mediated by nitric oxide (NO) derived from NOSs that may be activated by mediators other than histamine. The histamine-independent allergic conjunctivitis may be useful for analyzing mechanisms underlying chronic conjunctivitis.
 ...
PMID:Multiple cedar pollen challenge diminishes involvement of histamine in allergic conjunctivitis of Guinea pigs. 1464 73

The present investigation was conducted in order to determine whether lysophosphatidic acid (LPA) induces itch-scratch responses (ISRs) in mice. Intradermal administration of LPA induces ISRs; furthermore, the time course for LPA-induced ISRs was similar to that for histamine-induced responses. Comparative study of the pruritogenic activity revealed that histamine possessed a potent effect characterized by a dose-response relationship; however, prostaglandin D2 failed to induce this response. Pretreatment with ketotifen, a histamine H1 receptor antagonist, and capsaicin inhibited LPA-induced ISRs. Additionally, LPA-induced ISRs were abolished by Y-27632, an inhibitor of Rho-associated protein kinase (ROCK). These findings suggest that LPA-induced ISRs are attributable to histamine- and substance-P-mediated pathways. Moreover, the Rho/ROCK-mediated pathway may be involved.
 ...
PMID:Itch-scratch responses induced by lysophosphatidic acid in mice. 1529 55


1 2 3 4 5 Next >>