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At least 37 records · Page 2Linked to original sources

PubMed1978

Inhaled antihistamines--bronchodilatation and effects on histamine- and methacholine-induced bronchoconstriction.

To assess further the bronchodilator activity of inhaled antihistamines ten stable asthmatic subjects inhaled aerosols of clemastine, 1 mg/ml, and saline placebo administered double blind. Subjects underwent bronchial challenge with increasing concentrations of histamine and methacholine, and specific airways conductance was measured by whole body plethysmography at each concentration. There was a significant 21.9% increase in specific airways conductance after inhalation of clemastine. Subjects could tolerate significantly higher mean concentrations of histamine when treated with clemastine than with saline. The shift of the cumulative log histamine dose-reponse curve suggests that such protection is due to competitive antagonism to the inhaled clemastine. Clemastine did not protect subjects against methacholine-induced bronchoconstriction, which suggests that its bronchodilator properties are not related to any anticholinergic action.

Adult↗

PubMed1979

[An experimental and clinical study of the effect of ketotifen in the treatment of extrinsic bronchial asthma (author's transl)].

The therapeutic value of ketotifen (Zaditen), a new anti-allergic drug, was studied in patients with extrinsic bronchial asthma. a) In 8 persons the protective effect on bronchial provocation tests with allergen was examined 3 and 14 days after treatment and compared with cromoglycate (Intal); b) 19 patients were treated for 6 months with 2 x 1 milligram ketotifen (n = 7), 2 x 2 mg ketotifen (n = 7), 2 x 1 mg clemastine (Tavegil) (n = 5). The results were as follows: a) The amount of inhaled allergen causing a fall of 20% in FEV1.0/VC was 9-12 times larger with both therapeutic regimens. b) Ketotifen definitely improved the asthmatic symptoms as compared with clemastine. The improvement was independent of the dosage. Side-effects occurred more frequently with clemastine. The study confirms the in vitro demonstrated anti-analphylactic properties of ketotifen; that it can be taken by mouth is of particular clinical interest.

Asthma↗

PubMed1978

Clinical investigation of agents with prophylactic anti-allergic effects in bronchial asthma.

To determine the efficacy of ketotifen as an oral anti-asthmatic agent, experimental and therapeutic long-term trials were carried out. Four models were used in the expirmental therapeutic trials nad the antihistaminic agent clemastine and disodium cromoglycate were used as comparative substances. It was demonstrated that ketotifen provides protection against bronchopasm induced by allergens, histamine and exercise, but not against that induced by acetylcholine. In the therapeutic long-term trials, the efficacy and tolerance of ketotifen were compared with that of clemastine and disodium cromoglycate for a period of 6 months. In another study ketotifen was administered for 1 year. Ketotifen proved very effective in decreasing the frequency and duration of asthmatic attacks, concomitant medication could be reduced and the patients improved subjectively. From these trials it can be concluded that ketotifen is a safe and effective oral anti-anaphylactic agent for use in the long-term treatment of bronchial asthma.

Acetylcholine↗

PubMed1978

Performance studies with antihistamines.

1 Effect of four antihistamines, chlorpheniramine (4 mg), clemastine (1 mg), promethazine (10 mg) and terfenadine (60 mg), on visuo-motor coordination and on subjective assessments of performance and well-being were compared with placebo in six healthy females from 0.5--7.0 h after morning ingestion of each drug. The study was double-blind, and the doses used were believed to be equally potent in their antihistaminic activity. 2 There was impaired performance 1.5 h (P less than 0.01) after chlorpheniramine, 3.0 h (P less than 0.05) and 5.0 h (P less than 0.01) after clemastine, and 3.0 h (P less than 0.01) and 5.0 h (P less than 0.001) after promethazine. It was not possible to establish effects on performance after ingestion of terfenadine. Subjective assessments of performance were not altered. 3 The subjects as a group reported improved alertness (P less than 0.05) and improved wakefulness (P less than 0.05) 0.5 h and 3.5 h respectively after ingestion of terfenadine, and were less energetic (P less than 0.05) 7.0 h after ingestion of chlorpheniramine. There were not other consistent changes in assessments of well-being.

Adult↗

PubMed1978

The protective effect of ketotifen in bronchial asthma.

Thirty-six patients with confirmed allergic bronchial asthma were divided into 3 parallel groups and treated with ketotifen 1 mg b.i.d. (Group I), ketotifen 2 mg b.i.d. (Group II), and clemastine 1 mg b.i.d. (Group III) respectively for 6 months. Nine out of 12 patients in Group I and 10 out of 12 in Group II experienced a statistically significant improvement in dyspnoea and in pulmonary function (Tiffeneau test). Likewise there was a marked reduction in the number, severity and average duration (minutes per week) of asthmatic attacks. By the 12th week, 8 out of 12 patients in the clemastine group had dropped out because of inefficacy. Ketotifen was very well tolerated by all the patients. In both ketotifen groups pathological eosinophil counts returned to normal during treatment. It can be concluded that ketotifen is effective in the long-term prophylaxis of bronchial asthma.

Adolescent↗

PubMed1978

A repeated dose comparison of the side effects of five antihistamines on objective assessments of psychomotor performance, central nervous system arousal and subjective appraisals of sleep and early morning behaviour.

The side effects of five antihistamines (chlorpheniramine maleate, mebhydrolin, clemastine hydrogen fumarate, Tavegil; ketotifen, and promethazine hydrochloride) were measured on subjective assessments of sleep and the integrity of early morning behaviour and objective assessments of complex psychomotor behaviour and central nervous system arousal. Fifty consenting volunteers each received one of the five preparations for a period of four days with the subjective effects being reported on a set of 10 cm line visual analogue scales and the objective assessments being made via a computer assisted reaction time task and critical flicker fusion thresholds. Chlorpheniramine, 4 mg t.d.s. for four days, produces a significant impairment in critical flicker fusion thresholds with respect to pretreatment baselines but none of the preparations showed any significant impairment in complex reaction time assessments. The subjective assessments of sleep and early morning hangover showed mebhydrolin and clemastine to be free from detrimental side effects, but promethazine and chlorpheniramine produce significant impairments in the integrity of early morning behaviour.

Adult↗

PubMed1978

[Drug prevention of bronchial asthma: inhibition of histamine and exercise-induced asthma by a new anti-anaphylactic oral preparation (ketotifen) (author's transl)].

The protective anti-asthmatic effect of a new anti-allergic drug with histaminolytic and anti-anaphylactic properties was tested in various controlled clinical studies of induced bronchospasm in asthmatic patients (provocation tests using a histamine aerosol, and exercise-induced asthma using a bicycle ergometer). The drug, ketotifen (a cycloheptathiophene derivative) was compared with a classical antihistaminic (clemastine) and a known cell stabiliser (disodium cromoglycate). In both models ketotifen provided significant protection.

Adult↗

PubMed1977

Anti-asthmatic properties of a new peroral drug (HC 20-5II).

A clinical trial was performed with a new substance (HC 20-511) derived from the cycloheptothiophene group used in the management of asthma. Twenty-four asthma patients were treated at random, with HC 20-511 or placebo or the antihistaminic substance, clemastin (Tavegyl). A statistical evaluation of the results unequivocally demonstrates good protection with a single dose of 2.0 mg or two times 1.0 mg for 3 days against a challenging antigen, compared with the placebo or the antihistaminic agent. Tolerance was excellent.

Adolescent↗

PubMed1978

Inhibitory effects of imidazolines on histamine liberation from human leukocytes and on tracheal smooth muscle tone.

Antigen-induced IgE-mediated release of histamine from human leukocytes, an in vitro model of allergic reactions, was blocked by imidazole and imidazole-compounds such as oxymetazoline and clonidine. The H-2-antihistamines antagonized this effect of imidazolines. Alpha- and H-1-receptor blocking agents did not antagonize the effect. The contractile effects of the imidazolines were tested on tracheal preparations from the cow and guinea-pig. Imidazole was found to be a rather potent contracting agent, while oxymetazoline only caused weak contractions. Clonidine relaxed the tracheal muscles, when used in the concentration range which were inhibitory in the leukocyte experiments. The contractions caused by imidazolines were non-competitively inhibited by clemastine, while the relaxing effects were blocked by a combination of propranolol, phentolamine and cimethidine. The results suggest that imidazolines which inhibit histamine release and relax bronchial smooth muscles may be of therapeutic importance in the treatment of human allergic disorders.

Animals↗

PubMed1979

The effects of metiamide and H1 receptor blocking agents on anaphylactic response in guinea-pigs.

The effects of metiamide and of four H1 receptor blocking agents (mepyramine, promethazine, clemastine and ketotifene) on anaphylactic reaction were studied in the guinea-pig. The H1 blockers conferred partial protection which shows that with the experimental protocol utilized (challenge injection with high doses of antigen), histamine plays a lesser role than other mediators released or synthesized. Metiamide (30.0 mg/kg i.v.) noticeably enhanced the increase in pulmonary resistance observed during anaphylactic reaction and reduced the protective effect of the H1 antagonists on this parameter and on histamine release. These effects might be explained by an inhibition - at least partial - of the negative feed-back mechanism through which histamine controls its own release, or by a specific action of metiamide in high doses. The transient tachycardia initially observed in anaphylactic shock is partly related to stimulation of cardiac H2 receptors by the histamine released, since it is suppressed by metiamide.

Airway Resistance↗

PubMed2026

Hippocampal teneurin-4 knockdown promotes depression-like behavioral phenotypes by disrupting oligodendrocyte differentiation in mice.

Depression is one of the most prevalent mental disorders worldwide. The limited clinical efficacy of current antidepressants highlights identifying new therapeutic targets. Emerging evidence suggests that dysfunction of oligodendrocyte lineage cells contributes to the pathophysiology of depression. Teneurin-4 (Tenm4), a transmembrane protein that promotes oligodendrocyte differentiation and myelination, has been implicated in psychiatric disorders in genome-wide association studies; however, its causal role remains unclear. To determine whether Tenm4 contributes to depressive-like behavioral phenotypes, we examined Tenm4 protein expression in mice exposed to repeated forced swimming stress and generated hippocampal Tenm4 knockdown (Tenm4KD) mice. Chronic stress reduced Tenm4 expression levels in the hippocampus. Mice with hippocampus-specific Tenm4KD exhibited depressive-like behaviors, accompanied by reduced hippocampal myelin basic protein. Importantly, administration of clemastine, a myelin formation promoter, inhibited the reduction of myelin and attenuated depression-like behavioral phenotypes. Immunohistochemical analysis showed that Tenm4KD significantly decreased the number of mature oligodendrocyte cells and increased in the number of oligodendrocyte precursor cells, without changes in the total number of oligodendrocyte lineage cells. This study provides the first evidence that hippocampal Tenm4 deficiency induces depression-like behavior phenotypes through impaired oligodendrocyte differentiation and promoting demyelination. Our results identify Tenm4 as a molecular regulator of stress-induced behavioral phenotypes and suggest that it might represent a potential therapeutic target for mood disorders associated with demyelination.

Animals↗

PubMed1978

Inhibition of ultraviolet and phototoxic dermatitis in the mouse.

The effect of inhibitors on the inflammatory oedema elicited by medium-wave ultraviolet radiation (UVB) and long-wave ultraviolet radiation (UVA) in combination with chlorpromazine has been studied in the mouse, by means of a quantitative technique. Inhibition of the UVB reaction was observed with indomethacin, acetylsalicylic acid and betamethasone valerate, whereas the latter compound only was effective in the phototoxic state. No inhibition was obtained with hydrocortisone, phenylbutazone, epsilon-aminocaproic acid, polyphloretin phosphate, clemastin, alpha-tocopherol or ascorbic acid. With indomethacin and betamethasone valerate there was no inhibition at high doses when the compound was administered before UVB irradiation. These results are in accordance with a proposed central role for the prostaglandins in UVB inflammation. It is suggested that the phototoxic reaction to chlorpromazine may not be due to mediator action but rather to the effect of toxic photoproducts.

Animals↗

PubMed1975

Comparison of methods to study enzyme induction in man.

A combination of several in vivo parameters has been applied in male healthy volunteers to test the suitability of these parameters to indicate enzyme induction in man: Urinary excretion of D-glucaric acid and 6 beta-hydroxycortisol, activity of serum gamma-glut amyltranspeptidase, and pharmacokinetics of aminopyrine respond significantly to phenobarbital treatment. Glucaric acid excretion is enhanced about 7-fold. Its response to induction overcomes the large individual and inter-individual variations which exist in the untreated state for glucaric acid excretion and the other parameters applied, as well. Total body clearance of aminopyrine as obtained after an oral test dose increases more than twofold from 251 to 551 ml/min upon phenobarbital treatment. This arises from increases in both the elimination constant and the apparent volume of distribution, as well. Urinary excretion of aminoantipyrine during 24 hr is about doubled, whereas the elimination of acetyl-aminotipyrine is not much affected. 6 beta-hydroxycortisol excretion in urine and activity of serum gamma-glutamyltranspeptidase are significantly augmented to about 150% of control values. Half life times of phenobarbital measured after termination of treatment are in normal range, suggesting no self-induction of phenobarbital metabolism. Because of the complexity of drug metabolizing enzymes only a combination of different parameters reliably indicates alterations in this enzyme system by inducing agents.

17-Hydroxycorticosteroids↗

PubMed1978