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Two doses of triprolidine (2.5 mg t.i.d. and 1.25 mg t.i.d.) were compared with placebo in 32 patients suffering from allergic rhinitis. Triprolidine 2.5 mg t.i.d. was statistically significantly better than placebo (p less than 0.05) in reducing the symptoms of sneezing and eye irritation. Neither dose of triprolidine produced significant drowsiness during the second week of treatment.
1 Effects of brompheniramine maleate (4 and 12 mg) and triprolidine hydrochloride (2.5 and 10 mg) on visuo-motor coordination, and on subjective assessments of performance, well-being and sleep were each studied in six subjects at 0.5, 1.5, 3.0, 5.0 and 7.0 h after ingestion. The doses refer to immediate and sustained release preparations respectively. 2. Triprolidine hydrochloride (2.5 mg) had an immediate effect on performance which persisted to 3.0 h, and the sustained release preparation (10 mg) impaired performance from 1.5 to 5.0 h. Brompheniramine maleate (4 mg) impaired performance from 1.5 to 3.0 h, and the sustained release preparation (12 mg) impaired performance at 1.5 h. There were no consistent changes in the subjective assessments of performance, or of well-being and sleep. 3. The studies emphasize the variable effects of antihistamines on performance, and suggest that effects on performance of sustained release preparations may be similar to those of the usual form. Sustained release preparations may provide an advantage in clinical practice if the antihistaminic activity is prolonged.
1 Nasal airway resistance (NAR) was measured by anterior rhinometry in ten volunteers with allergic rhinitis. Measurements before and after challenge with three concentrations of histamine diphosphate showed significant rises in NAR for each challenge. 2 In a double-blind, crossover study with the same patients triprolidine (2.5 mg) and pseudoephedrine (60 mg) were shown to be equally effective in reducing the rise in NAR produced by histamine challenge to one nostril; both were significantly better than placebo. 3 The rise in NAR of both nostrils after histamine challenge to one nostril was significantly reduced after pseudoephedrine compared with placebo. This suggests that pseudoephedrine is effective in preventing reflex mucosal congestion in the unchallenged nostril. 4 No increase in the pulse rate or blood pressure of the volunteers was detected after either drug.
The effects of q.i.d. administration of 60 mg pseudoephedrine (Sudafed) tablets or pseudoephedrine-triprolidine (Actifed) tablets after 5 d of medication were measured on tests of night vision, color perception, stereopsis, and reaction time. Neither drug appeared to impair performance.
In a double-blind crossover trial of pseudoephedrine 60 mg. and triprolidine 2.5 mg. alone and in combination, on 40 volunteers suffering from allergic rhinitis, both drugs were found superior to placebo in reducing the effects of allergic rhinitis and were of equal efficacy. The combination tablet was consistently better than either drug in several of the assessments and was the treatment which the subjects, as a whole, preferred. Side effects were not a problem with any of the medications.
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1. Burimamide, metiamide, chlorpheniramine, triprolidine and cocaine, were tested as inhibitors of histamine uptake and metabolism in the guinea-pig atrium and in mouse neoplastic mast cells. 2. Cocaine did not affect the uptake and metabolism of histamine, either in the atrium or in the mast cells. All the antihistamines tested blocked the uptake and metabolism of histamine in both preparations. The order of potency was burimamide greater than chlorpheniramine greater than triprolidine greater than metiamide in the atrium; and burimamide greater than metiamide greater than triprolidine greater than chlorpheniramine, in the mase cells. 3. Comparison of the present results with the antihistamine activity of these blocking agents suggests that no correlation exists between the receptor blocking activity and the ability of these substances to act as inhibitors of histamine uptake and metabolism.
A permeability factor was extracted in a latent form from guinea pig skin and separated by ammonium sulfate fractionation into the pseudoglobulin fraction (30--50% saturation). The activation of the latent form of the permeability factor seemed to be caused in the desalting step by gel filtration with Sephadex G-50. The factor was partially purified by streptomycin treatment and column chromatography using hydroxyapatite, diethylaminoethyl cellulose and Sephadex G-75, in this order. Gel filtration showed that its molecular weight was approx. 35000. Its permeability activity was heat stable at 61 degrees C for 60 min at neutral pH, resistant at pH 5--10 and at ionic strengths from deionized water to 1 M NaCl at 4 degrees C. Its activity was transient and suppressed by guinea pig serum, but insensitive to an anti-histamic agent (triprolidine). Furthermore, its permeability activity was inhibited by diisopropylfluorophosphate, soybean trypsin inhibitor and leupeptin, and completely adsorbed by soybean trypsin inhibitor affinity column. These findings suggested that the permeability factor was a serine-type protease.
Studies are not available to support the common use of alpha-adrenergic agents and/or antihistamines in the treatment of acute otitis media. A total of 378 patients with acute otitis were entered in a double-blind study comparing treatment results with antibiotics and either placebo, pseudoephedrine, triprolidine, or a combination of these; 196 patients returned. Age and return rate did not differ among groups. Cure rates and duration of fever were the same for each group. The cost and possible side effects of these agents, added to their lack of beneficial effect in otitis, should interdict their use.
The vasodilator action of CV-705 was investigated in a number of vascular regions of anesthetized mongrel dogs and this action was compared with that of papaverine. When CV-705 was administered intravenously the vertebral, common carotid and internal carotid blood flow was increased considerably and was long-lasting. These effects were most remarkable among the regions tested. Femoral, aortic and coronary blood flow were also increased. On the other hand, the blood flow through superior mesenteric artery and portal vein increased only slightly. Renal blood flow was decreased slightly after an intravenous administration, whereas an increase was observed after an intra-arterial administration. Such a regional distribution of blood flow after CV-705 was quite similar to that observed with papaverine. CV-705 was well absorbed through the digestive tract. CV-705 given intravenously showed a weak hypotensive and positive chronotropic action. The increase in common carotid blood flow induced by intra-arterial administration of CV-705 was not affected by pre-treatment with atropine or triprolidine, but was partially suppressed by pre-treatment with propranolol. These results suggest that CV-705 has a papaverine-like action as well as a weak beta-adrenoceptor stimulating action, consequently a vasodilator action occurs.
In order to investigate the mechanism of late asthmatic response (LAR), inhibitory effects of various drugs for LAR were examined in two wheat flour-sensitive asthmatic subjects who showed immediate and late responses in the allergen provocation test and skin test. Antihistamines did not inhibit the LAR but totally or partially inhibited the immediate response. By contrast, corticosteroids inhibited the LAR but not the immediate response. Disodium cromoglycate inhibited both responses. Diethyl carbamazine citrate, an inhibitor of release of SRS-A, seemed to shorten the duration of the LAR, although it has no effect on the immediate response and/or on the severity of the LAR. Indomethacin and acetyl salicylate, which inhibit prostaglandin synthesis, had no significant effects on either the immediate or the LAR.
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Glue ear is a common condition in childhood. In this report treatment by Bisolvon and Actifed is described. In 60 patients, a success rate of 90% was recorded.
A study was made of the effect of anit-histamine, antiserotonin and of different anti-anaphylactic drugs on PCA reactions induced in mice with IgG1 or IgE. Further, using the ability of mouse IgE to sensitize rat mast cells, a comparative study was also made of PCA reactions induced in mice and rats with mouse IgE. Antihistamines produced a partial inhibition of PCA reactions induced in mice with mouse IgG1 or IgE and in rats with mouse IgE whereas antiserotonin inhibited PCA reactions induced in rats with mouse IgE, but had no effect on PCA reactions induced in mice with mouse IgG1 or IgE. The simultaneous use of antihistamine and antiserotonin resulted in a total inhibition of PCA reactions induced in mice with IgG1 and in a marked but not total inhibition of PCA reaction due to IgE; PCA reactions induced in rats with mouse IgE were totally inhibited. Compounds known to change the intracellular level of cyclic AMP were found to have little or no effect on PCA reactions induced in mice with either IgG1 or IgE in spite of producing a complete marked inhibition of PCA reactions induced with mouse IgE in rats. Diethylcarbamazine or disodium cromoglycate were also very effective inhibitors of rat PCA reactions induced with mouse IgE although having no effect on PCA reaction induced in mice with this same antibody or with IgG1. Thus, in spite of sharing common mediators released from the same type of target cell sensitized with the same type of antibody, PCA reactions induced in mice and rats with mouse IgE reacted very differently to the pharmacological effect of most of the drugs tested. This fact seems to indicate that the physiological mechanism operating in mouse mast cells are different from those operating in rat mast cells.
The effects of antihistamines, steroids and disodium cromoglycate on an immediate hypersensitivity reaction in the guinea pig eye are described in terms of clinical observations, histological examinations of sections of eyes and cytological studies of material from the conjunctival surface. The use of brushes to sample the cells on the conjunctival surface is described. The effect of repeated daily challenges on the reaction is also reported.
Decongestants and antihistamines are known to produce effects capable of adversely modifying physiological function and psychomotor task performance. Because of relevance to safe pilot performance, the effects of single doses of two decongestant-antihistamine preparations (Compound A and Compound B), or a placebo on cardiorespiratory responses to two equally spaced +2 Gz tests during separate 2-h exposures at 388 m (1,274 ft MSL) ground level (GL) and 3,810 m (12,500 ft) chamber altitude were assessed. Post-altitude fatigue was assessed by cardiorespiratory responses to submaximal bicycle ergometry. Compound A and Compound B appeared to exert no significant detrimental effects on short-duration post-altitude ergometric fatigue-ability. With two exceptions, all combinations of medication, altitude, and +Gz were well tolerated. Two subjects were clearly incapacitated during the first +2 Gz test under Compound A at 3,810 m (12,500 ft) altitude. It is felt that the +Gz-intolerance resulted mainly from an adverse interactive effect of Compound A and altitude on vasomotor and/or chronotropic mechanisms.
Fourteen men were studied to determine the combined effects of two altitudes--388 and 3,810 m or 1,274 and 12,500 ft--and three preparations--lactose placebo, Compound A (Actified, and Compound B (Dristan). Subjects reported least attentiveness with A and greatest with placebo. Fatigue increased significantly with time while energy, interest, and attentiveness decreased. The Multiple Task Performance Battery (MTPB) showed no effects of altitude, drugs, or time on overall performance; however, performance declined with time in several tasks, while problem solving improved. Subjects enjoyed the problem-solving tasks and may have given them preference as levels of interest declined. Though the MTPB overall composite scores did not change significantly, physiological parameters and subjective evaluations indicate that type of compound and time after ingestion are important. Declines in energy and attentiveness 2.5 h after ingestion could result in neglect of important--although routine--tasks. Hypoxia might enhance this effect and consequences might be worse in subjects whose medical conditions require these drugs.