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The effect of an antiallergic (antihistaminic and antiserotonin) drug bicarphen on the functional state of the central nervous system (CNS) was studied. In experiments on animals bicarphen in contrast to dimedrol (diphenhydramine) exerted predominantly the activating effect on CNS (decreased the hypnotic action of barbamyl, enhanced the summation capacity of CNS and the activity of mice in the escape behavioral test, increased the bioelectrical activity of the brain and the activating effect of antidepressants on the EEG).

In experiments on 183 rats it was shown that cordarone, anapriline, dimedrol and riboxine increasing in experimental cardiac insufficiency tolerance to the cardiotoxic effect of strophanthin differ significantly by their influence on the hemodynamic effects of this cardiac glycoside. Cordarone increased intensity of the hemodynamic effects of strophanthin and accelerated their development. Under the action of anapriline and dimedrol the stimulating effect of strophanthin on hemodynamics decreased to a much lesser degree than its cardiotoxicity. Riboxine virtually abolished the hemodynamic effects of strophanthin.

The time-course of the antiexudative effect of the antihistaminic drugs diphenhydramine, phencarol and suprastin was studied in experimental dextran edema of the rat hind limb after intragastric administration of the drugs in a dose of 50 mg/kg. The data obtained were correlated to the time-course of the blood serum drug concentration measured by high pressure liquid chromatography. The relationship between the pharmacological action of the drugs and the mean maintenance dose was depicted by means of computer. It has been shown that the antiexudative activity of diphenhydramine and phencarol is approximately identical, whereas the efficacy of suprastin is several times less.

Histamine and dimedrol exerted in vitro inhibitory effects on endotoxin-induced platelet aggregation. When administered at high concentrations pyrilamine potentiated aggregating influence of endotoxin. The experimental results indicate difference in effects of dimedrol and pyrilamine falling into the same group of H1-blockers in relation to induced platelet aggregation.

Tests were conducted on mice of the CBA line, immunized through a single intraperitoneal administration of 0.5 ml of a 5% sheep erythrocytes suspension. Antihistaminic agents were introduced by the intraperitoneal route in a dose of 5 mg/kg, first at one time and then repeatedly at various intervals with respect to the initial immunization benadryl and diazoline, when administered in a single dose to mice 24 hours after immunization activated the primary immune response to sheep erythrocytes, whereas phenergan and ethisine manifested merely a tendency toward activation of the immunogenesis. The drugs under study failed to have any significant effect on the titres of serumal hemolysines and hemaglutinines.

Toxic and pharmacological properties of promedol, droperidol and dimedrol were studied during burn shock and combined radiation and thermal injury (CRTI). Acute toxicity and analgesic effect of promedol were shown to increase in the given period Droperidol analgesic effect enhanced in burn and CRTI, cataleptic action enhanced only in CRTI. A decrease of antihistaminic activity of dimedrol was more pronounced in CRTI.

As compared to the action of the drugs given alone, the combinations of antiallergic drugs and cardiac glycosides had different effects on the nature and intensity of the processes inherent in allergy. These differences correlated to a certain degree with the mechanism of a reaction which experienced the action of the drug combination. Within the frames of synergoantagonism interplay, the drug combination produced on some of the reactions an effect which was similar to that exerted by one of the components. Meanwhile the magnitude of the effect produced by the same drug combination on the other reactions was half as that manifested by the components administered alone. Sometimes in the combinations of the drugs, the effects of the constituent parts were perversed in the course of action on some of the processes. In individual cases the combined drugs had remarkable effects on a reaction, while the individual components did not change it. Strophanthine given in the combinations tested, almost never displayed its specific action on the reactions inherent in sensitization. Combined diphenhydramine affected, as a rule, the sensitization and altered the effect of other substances.

The antihistaminic and antiserotonin properties of 16 new tropine esters, analogues of atropine, tropacin and tropaphen, were studied. All of them were found to lessen the spasmogenic effects of histamine and serotonin. The intensity of the antihistaminic and antiserotonin action of the drugs varied depending upon the structure of the radical at the alpha-carbon atom in the acidic part of the molecule. Both types of the activity are most marked in the desoxymethyl propyl and butyl analogues of atropine. The absence of the oxymethyl group at alpha-carbon in the series of atropine analogues is shown to facilitate the manifestation of the antihistaminic activity.

A high antihistaminic activity of quinuclidyl-3-diphenylcarbinol (phencarol) has been ascertained. In pharmacological experiments phencarol is superior to dimedrol (diphenhydramine), both as concerns its antihistaminic activity and the duration of its action. Unlike dimedrol and diprazine (promethazine) it has no inhibitory effect on the central nervous system. With its clinical use phencarol is effective in treating urticaria, Quincke's edema and allergic skin reactions. The drug is well tolerated by the patients and does not produce any inhibitory or soporific action. Phencarol has an authorized permission to be used for medical purposes.

In the experiments on male albino rats absorption of dimedrol, pipolphen and suprastin from the small intestine was studied in vitro by the method of "turned sacks". It was shown that immunization of the animals with ovalbumin in combination with Freund's incomplete adjuvant does not influence significantly absorption of the antihistaminic agents in the rat small intestine in vitro. During anaphylactic shock absorption of pipolphen and to a lesser degree of suprastin tends to increase. The structure of the absorbing surface of the intestinal mucosal epithelium is of importance for absorption of dimedrol and to a lesser degree of pipolphen. Absorption of the antihistaminic agents in the rat small intestine in vitro depends on the activity of the drug metabolizing enzymes that especially distinctly shows up for pipolphen. Induction of the metabolizing enzymes by phenobarbital contributes to an active elimination of the agents from the incubation medium. Absorption of dimedrol and suprastin is implemented through an active transport whose energy supply for dimedrol is related to a greater extent to anaerobic processes of oxidation and for suprastin both to aerobic and anaerobic processes.

Histamine was found to suppress the myocardial contractile function, to decrease systemic arterial blood pressure and to exert a positive chronotropic effect in unanesthetized dogs. A preliminary blockade of H1-receptors prevented the hypotensive effect of histamine, blockade of H2-receptors prevented the development of the positive chronotropic effect.

The effect of antihistaminic drugs, histamine and their combinations on the development of anaphylactic shock and the period of repeated resolution doses was studied in rabbit experiments. It was established that administration of dimedrol during sensibilization aggravated while diazolin and histamine attenuated the course of anaphylactic shock and periods of repeated resolution injections. Simultaneous administration of antihistaminic agents and histamine enhanced the allergization of the body. Under conditions reported dimedrol prevented hypertrophy of the adrenals that occurred in response to sensibilization. Meanwhile diazolin did not interfere with the reaction development and histamine stimulated it. Combined administration of the antihistaminic agents and histamine provoked an inhibition of the above reaction of the adrenals to body sensibilization.

The effect of dimephosphon on the development of the experimental inflammatory edema (agar-, dextran- and carrageenan-induced edema) of rat and mouse paws was compared with those of voltaren and dimedrol. The anti-inflammatory activity of dimephosphon occurring on account of the antiexudative component was established. The antihistamine and antiserotonin activity of dimephosphon was shown on models of paw edema caused by subplantar administration of mediators and modulators of inflammation. The drug exerts no influence on similar effects of bradykinin and prostaglandin E2, intensifies edema-inducing action of prostaglandin F2 alpha. The involvement of the anti-inflammatory component in the therapeutic effect of dimephosphon is suggested.

Antihistaminic (H1) drugs pipolphen, suprastin and dimedrol are characterized according to absorption through human oral mucosa and distribution between phosphate buffer solution and organic solvents at various medium pH values. Their constants of ionization and coefficients of distribution in the n-octanol--phosphate buffer system, pH 7.4, as well as the bound fraction at the interaction of these drugs with human serum albumin were determined. The relationship between absorption through human oral mucosa of antihistaminic drugs and the hydrophobic character of their molecules and constants of ionization was found. An attempt was made to predict for them on the basis of the authors' own results and literature data possible pharmacokinetic and pharmacodynamic behavior in the organism.

It has been established by equilibrium dialysis and ultraviolet difference spectrophotometry that at pH 6.8 diphenhydramine interacts with human serum albumin more actively. It has been demonstrated that on the molecule of human serum albumin diphenhydramine interacts with two types of independent binding sites. The effects of pH and ionic strength of the medium, temperature, and cations on diphenhydramine binding with human serum albumin indicate that the drug is bound by hydrophobic interaction to the first type of the binding site and by van der Waals' forces to the second type of the binding site. Interaction of diphenhydramine with the second type of the binding site involves B conformation of human serum albumin. The presence of histamine increases diphenhydramine binding to human serum albumin via the second type of the binding site.

Histochemical and morphometric analysis of mast cells of the gastric and duodenal mucosa of rats given dyphenhydramine and suprastin for a long period of time (up to 45 days) revealed an increase in their functional activity that manifested in the enhancement of the processes of neoformation and maturation of juvenile mast cells and in the increased break down of mature cellular forms.

It was shown by the in situ method that absorption of dimedrol, pipolphen and suprastine from the small intestine of the rats immunized parenterally with ovalbumin against the background of intravenous administration of the resolving dose of ovalbumin significantly decreased in connection with the formation in the immunized rats of antiovalbumin antibodies. Administration of euphylline simultaneously with the resolving dose of ovalbumin to the immunized rats partially normalized absorbability of all three drugs.