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At least 937 records · Page 52Linked to original sources
PubMed1985

[C-2 basically substituted thiazoles with H2-antagonistic action. 21. H2-antihistaminics].

In studies on structure-activity relationships of histamine H2-receptor antagonists, C-2 basically substituted thiazoles were prepared and tested for their H2-antihistaminic activity on the isolated guinea-pig atrium and on the histamine stimulated acid secretion of the anaesthetized rat. As a basic substituent the dimethylaminomethyl group is especially suitable, while cyclic guanidines lead to lower H2-antagonistic activity.

Animals↗
PubMedDate not supplied

[Preclinical study of the safety of the antihistaminic preparation dimebon].

The antihistaminic drug dimebon was subjected to toxicological study. It was demonstrated that as regards the level of the mean lethal doses dimebon can be attributed to little toxic substances. Administration of the drug in the doses approximating the therapeutic ones (1 and 5 mg/kg) for 2 months did not produce any alterations in rats, guinea-pigs or dogs. When administered in high doses (10 and 70 mg/kg) the drug provoked compensated abnormalities of some functions of the liver and kidneys in the presence of moderate and reversible structural changes in these organs. Dimebon did not exert any local irritating effect on the gastrointestinal tract. Administration of the drug in doses of 150 and 300 mg/kg at different times of pregnancy (days 1-7, 8-13, 14-19) did not produce any embryolethal or teratogenic effects.

Abnormalities, Drug-Induced↗
PubMed1976

Immediate hypersensitivity in the guinea pig conjunctiva. II. Effect of treatment with antihistamines, steroids and disodium cromoglycate.

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.

Animals↗
PubMed1985

[Isohistamine and homologs as components of H2-antagonists. 22. H2-antihistaminics].

Starting with isohistamines and their homologues or from appropriately hydrogenated imidazo[1,2-c]pyrimidines, imidazo[1,2-c] [1,3]diazepines and -diazocines, H2-antihistaminics with cyanoguanidine and 2-nitro-1,1-ethenediamine structure were prepared and tested for their H2-antagonistic activity on the isolated guinea-pig atrium and on the histamine-stimulated acid secretion of the anaesthetized rat. While the cyanoguanidines 3a-c,f were weaker in comparison to cimetidine, or inactive, 12a-e,g-l, 17 and 19 possessed markedly stronger activity, whereby the activity reaches a maximal effect at the rat stomach when cyanoguanidine and imidazole ring are connected with a three-membered chain. The activity of the 2-nitro-1,1-ethenediamines 15b,h,l exceed that of the comparable cyanoguanidines at both test models.

Animals↗
PubMed1986

Effects of antihistamines and local anesthetics on excess tachycardia in conscious dogs.

Atropine produces cardioacceleration in conscious dogs partly by reversing the pre-existing parasympathetic cardioinhibition and partly by inducing "excess tachycardia" (ET). Because ET occurs independently of adrenergic mechanisms, the present study sought to determine whether ET is generated by a positive chronotropic action of endogenous histamine on pacemaker cell H1 receptors. ET was antagonized in conscious dogs by the H1-receptor antagonists pyrilamine, diphenhydramine, chlorpheniramine and promethazine (1-5 mg/kg i.v.), but not the H2-receptor antagonist cimetidine (2-10 mg/kg i.v.). Pyrilamine (0.1 mg/kg i.v.), but not cimetidine (4 mg/kg i.v.), also eliminated a histamine tachycardia (31 +/- 4.1 beats/min) produced by injecting histamine (22 +/- 14.2 micrograms) into the sinus node artery after pharmacological autonomic blockade. The 30-fold greater dose of pyrilamine required to antagonize ET than histamine tachycardia suggests a nonantihistaminic, and possibly a local anesthetic mechanism of action on ET. Indeed, lidocaine, procaine, propranolol and pyrilamine antagonized ET in doses corresponding to the known relative local anesthetic potencies of these agents. The same doses of pyrilamine, lidocaine and procaine had significantly less effects on a comparable beta adrenergic tachycardia produced by intravenous isoproterenol infusion (0.1-0.5 micrograms/kg/min i.v.) after hexamethonium (10 mg/kg i.v.). The results indicate that H1-receptor blockers antagonize ET because of their local anesthetic effects and not their antihistaminic properties. The results also suggest that the ionic pacemaker mechanisms generating ET and beta adrenergic tachycardia are different.

Anesthetics, Local↗
PubMed1986

[Synthesis and H2-antagonistic action of N3, N5-substituted 1,2, 4-oxadiazole-3, 5-diamine. 26. H2-antihistaminics].

N5-(3-[3-(1-Piperidinylmethyl)phenoxy) phenoxy]propyl)-1,2, 4-oxadiazole-3, 5-diamines and N5(2-[(5-dimethylaminomethyl-2-furanyl) methylthio] ethyl)-1,2,4-oxadiazole-3,5-diamines with different N3-substituents were prepared and tested for their H2-antihistaminic activity on the isolated guinea-pig atrium. They were synthesized by nucleophilic substitution of the appropriate 5-trichloromethyloxadiazoles with the amines 3 and 11. Of the prepared substances 10a,c in particular showed high H2-antagonistic activity.

Animals↗
PubMedDate not supplied

Microbial transformation of the antihistamine pyrilamine maleate. Formation of potential mammalian metabolites.

Fourteen fungi were found to metabolize pyrilamine (2-[(2-dimethylaminoethyl)(p-methoxybenzyl)amino]pyridine). Two Cunninghamella elegans strains transformed essentially all of the pyrilamine added after 144 hr. After 48 hr of incubation, C. elegans ATCC 9245 metabolized 76% of the antihistamine into methylene chloride-extractable pyrilamine metabolites. These organic-soluble metabolites were isolated by HPLC and the major metabolites were characterized by comparison of their chromatographic, mass, and 1H-NMR spectral properties with those of authentic compounds. The major metabolite was identified as 2-[(2-dimethyloxyaminoethyl)(p-methoxybenzyl)amino]pyridine (N-oxide derivative of pyrilamine). Other metabolites identified were 2-[(2-dimethylaminoethyl)(p-hydroxybenzyl)amino]pyridine, 2-[(2-methylaminoethyl)(p-methoxybenzyl)amino]pyridine, and 2-[(2-methylaminoethyl)(p-hydroxybenzyl)amino]pyridine. These metabolites represent O-demethylated, N-demethylated, and O- and N-demethylated derivatives of pyrilamine, respectively. The mutagenic activities of the N-oxide and the N- and O-dealkylated pyrilamine derivatives, and pyrilamine maleate were measured by reversion of Salmonella typhimurium strains TA97, TA98, TA100, and TA102. Pyrilamine maleate and the three microbial metabolites showed no appreciable mutagenic activity in any of the S. typhimurium tester strains. The metabolism of pyrilamine by 12 other filamentous fungi and yeast strains was much less when compared to C. elegans and ranged from 3.8% to 12.2%. The fungal metabolism of pyrilamine may be useful in predicting results of mammalian metabolism and in readily providing sufficient quantities of metabolites for further toxicological studies.

Aminopyridines↗
PubMedDate not supplied

H-1 blockers--classical antihistamines.

The H1-blocking antihistamines pharmacology, pharmacokinetics, uses, toxicity and special precautions are presented. Newer agents may offer advantages of longer half-life and lower levels of sedation and motor impairment. Therapeutic considerations are listed with attention to sustained therapeutic efficacy.

Histamine H1 Antagonists↗
PubMed1987

Antihistamines, drowsiness, and psychomotor impairment: central nervous system effect of cetirizine.

Altered central nervous system function as indicated by drowsiness and impaired psychomotor performance is often a consequence of the use of traditional antihistamines. Demonstration that newer agents lack these CNS effects requires quantitative and objective measurements that are sensitive enough to assess the psychomotor capabilities required for such activities as driving an automobile. These capabilities include extended attention span, vigilance, visual tracking, rapid information processing, and reaction time. We have used several psychomotor function tests to conduct two investigations assessing the CNS effects of cetirizine. In the first study, 12 healthy, atopic subjects received single oral doses of hydroxyzine 25 mg, cetirizine 10 mg and 20 mg, and placebo in a double-blind, four-way crossover study. Skin-wheal response to intradermal histamine, psychomotor effects, and serum concentrations of each drug were measured for 36 hours after each dose. The CNS effects were measured using critical flash-fusion frequency tests and Stroop word testing. Perceived feelings of drowsiness were measured using a visual analogue scale (VAS). In the second study, 15 healthy subjects received single oral doses of diphenhydramine 50 mg, cetirizine 5 mg, 10 mg, and 20 mg, and placebo in a double-blind, five-way crossover study. Skin-wheal response to intradermal histamine, psychomotor effects, and serum concentrations of each drug were measured for 24 hours after each dose. The CNS effects were measured using digit-symbol substitution testing. "Trails-B" maze tracking, and an analyzer of driving performance that assessed reaction time and vigilance.(ABSTRACT TRUNCATED AT 250 WORDS)

Automobile Driving↗
PubMed1987

Effects of antihistamines on the spinal reflex in rats.

The effect of antihistamines on the spinal reflex in rats was studied. When H1-blocking agents such as pyrilamine, promethazine and diphenhydramine were given intravenously, both monosynaptic reflex (MSR) and polysynaptic reflex potentials (PSR) were inhibited in a dose-dependent fashion without affecting the dorsal root reflex and dorsal root-dorsal root potential. The extent of suppression of the MSR and PSR measured in spinal rats was smaller than that of intact rats. When H1-blocking agents (0.25-5.0 nmol) were applied by intraspinal microinjection close to the motoneuron, the MSR and PSR were depressed dose-dependently. Simultaneous application of carbachol partially blocked the inhibitory effects of H1-blocking agents induced by intraspinal microinjection. Also, the motoneuron discharges evoked by microinjection of glutamic acid or acetylcholine were depressed by simultaneous administration of any of H1-blocking agents tested. However, H2-blocking agents, such as cimetidine and ranitidine, given either intravenously or intraspinally had a scarcely measurable effect on the spinal reflex. The depression of H1-blocking agents on the spinal reflex is due to a direct inhibition of the motoneuron on the one hand. On the other hand, there is also an involvement of higher centers in the central nervous system increasing potential depression.

Animals↗
PubMed1988

A multicenter, open study of the non-sedating antihistamine, terfenadine (Seldane), in the maintenance therapy of seasonal allergic rhinitis.

A multicenter open study was conducted throughout the 1984 fall pollen season to assess the possible development of tolerance or loss of efficacy to terfenadine in the maintenance therapy of patients with seasonal pollinosis. Patients with proven allergic pollinosis were entered into a 1-week initial treatment period taking terfenadine 60 mg bid and only those who responded to the initial treatment with "moderate" to "complete" relief continued on terfenadine throughout a 4 to 11-week pollen season for evaluation of continued efficacy. A total of 179 patients from five study centers were enrolled in the initial treatment period and 154 (86%) responded to terfenadine with "moderate" to "complete" relief of symptoms. Of these 154 patients who continued terfenadine treatment, approximately 90% of the patients maintained the same degree of relief throughout the pollen season. All symptoms of seasonal pollinosis including nasal congestion improved significantly the first day of treatment. This improvement in symptoms continued during the first week and remained unabated throughout the pollen season. The incidence of adverse events was low with sedation being reported by only 2.8% of patients at some time point during the study. It is concluded that terfenadine is a safe and effective non-sedating antihistamine in the maintenance therapy of seasonal allergic pollinosis and that tolerance is not noted during continued administration.

Adult↗
PubMed1988

Inhibition of skin reactivity by antihistamines.

A number of studies have explored the inhibition of antigen-induced skin hypersensitivity reactions by the newer, nonsedating antihistamines such as terfenadine. The collective results of these studies indicate that this inhibitory effect begins within two hours of the administration of a single dose of terfenadine and within three to four days of a single dose of astemizole. Offset of this effect occurs within forty-eight hours of cessation of terfenadine therapy and four weeks or more after the withdrawal of astemizole. The time of onset and offset of this inhibitory effect is indicative of the period of clinical activity of these drugs and thus may be a relevant consideration in selecting an appropriate therapeutic regimen.

Astemizole↗
PubMed1988

Interaction of two barbiturates and an antihistamine on body temperature and motor performance of mice.

As an example for a drug combination used as a sedative (Vesparax) the actions of secobarbital (S), brallobarbital (B) and the antihistamine etodroxizine (E) were studied in mice after single and concomitant oral application. S and B caused a dose-dependent increase of exploratory locomotor performance enclosing a short period of locomotor depression. Such excitatory effect was suppressed by concomitant application. E produced a decrease in locomotion and--when added to S and B--enhanced their sedative effects. Explorative rearing was suppressed by low doses of S and B, by B, by E, and by all the combinations, whereas high single doses of S and B (20 mg/kg and 25 mg/kg, resp.) caused a triphasic temporal pattern. Motor coordination was investigated by means of fixed-bar and rotarod procedures. Increasing doses of S and B impaired motor performance within a small dose range. In concomitant applications rotarod performance revealed a dose-additive synergism whereas the effect was moderately superadditive in the fixed-bar test. Neither in single applications nor in combinations E showed any effects. Rectal temperature was poorly affected by the single drugs, but hypothermia was strongly enhanced by concomitant application of S and B and further potentiated by addition of E. The results suggest that responses to combinations of drugs even belonging to the same category cannot sufficiently be deduced from the single components alone.

Animals↗
PubMed1986

[Compensatory growth of the kidney. Effects of 3 antihistaminic drugs].

The compensatory growth of the kidney (C. G. K.) in the rat, is accompanied by a lowering of the renal concentration of histamine (507 micrograms/kg 48 hours after the beginning of the C. G. K. against 1,070 micrograms/kg in the normal kidney). Three antihistamines were injected i.p. during the first 48 hours of the C. G. K.: dexchlorpheniramine (H1 antagonist), cimetidine (H2 antagonist) and doxepin (both H1 and H2 antagonist). The C. G. K. was significantly lowered only in the rats that had been treated with doxepin in doses of 0.3 and 1 mg/kg/24 h. None of these treatments altered the histamine concentration in the kidney 48 hours after the beginning of the C. G. K. The action of doxepin might pass through mechanisms other than its anti-histaminic activity.

Animals↗
PubMed1987

Safety and efficacy of loratadine (Sch-29851): a new non-sedating antihistamine in seasonal allergic rhinitis.

Loratadine, a new antihistamine in the non-sedating class, was evaluated for efficacy and safety in treatment of allergic rhinitis in a multicentered study. Loratadine was found to be both safe and efficacious. When administered to patients with seasonal allergic rhinitis, a single daily oral dose of 10 mg is comparable in efficacy to clemastine, 1 mg, given twice daily. The incidence of sedation with loratadine is comparable to placebo and significantly lower than with clemastine. The incidence of anticholinergic side effects with loratadine is low and in this study was comparable to placebo and clemastine.

Capsules↗
PubMed1988

[Hypostamine (tritoqualine), a synthetic reference antihistaminic].

The role of histamine in hypersensitivity reactions justifies the use of antagonistic medication. The symptomatic action of the antihistamines has led many workers to forget the role of the drug in reducing histamine (hypohistaminic), in which interest should remain as a curative and mainly preventive medication. The main indications for the action of this drug at the level of physiopathological mechanism involved are: disorders that implicate the production of endogenous histamine, prevention of histamine release, reduction of over-production of histamine by regulation of receptor saturation, symptomatic action without side effects.

Biological Assay↗
PubMed1978

Effects of ovine hydatid cyst fluid in sheep before and after treatment with hydrocortisone, antihistamines and atropine.

The cardiovascular and respiratory responses to scolex-free ovine hydatid cyst fluid were studied in 65 sodium pentobarbital-anesthetized sheep. The arterial blood pressure (ABP), central venous pressure (CVP), stethogram and electrocardiogram were recorded. Intra-venous administration of 10 ml or less hydatid fluid brought about moderate to severe fall in ABP and rapid respiration or permanent respiratory cessation in majority of the animals. Forty six percent of the sheep died of circulatory and respiratory failure after the first injection or the hydatid fluid. Boiled hydatid fluid did not lose its potency to evoke the above responses. Hydrocortisone, given 200 mg daily for seven days, failed to prevent the reactions to hydatid fluid. Intravenous administration of the antihistamines chlorpheniramine, 4 mg/kg, and antazoline, 5 mg/kg, caused only partial prevention of the responses in 8 out of 15 responsive sheep. Pretreatment of the animals with atropine, 0.5--1 mg/kg subcutaneously, did not block the reactions. The cardiovascular and respiratory responses to ovine hydatid fluid may be due to antigen-antibody reactions or some toxic component of the fluid.

Animals↗