[Antiulcer activity of furoxanopyrimidine derivatives]. / Protivoiazvennoe deistvie proizvodnykh furoksapirimidina.

A series of four new furoxanopyrimidine derivatives was synthesized and studied with respect to antiulcerous, antisecretory, and antibacterial activity. Two compounds exhibit antiulcerous effect not accompanied (in contrast to the well-known H2 receptor blockers, quiditene, and other antiulcerous drugs) by inhibition of gastric acid secretion. No one of the studied compounds exhibited antibacterial activity in the tests with Helicobacter pylori.

[An experimental study of the antisecretory and antiulcer activities of kviditen]. / Eksperimental'noe issledovanie antisekretornoi i protivoiazvennoi aktivnosti kviditena.

Quiditene-(qunuclidyl-3)-di-(thyenel-2)carbinole hydrochloride was studied by using various experimental models. The agent was compared with H2-blockers. When gastrically used, quiditene in doses of 5-50 mg/kg dose-dependently decreased gastric acid secretion and prevented acute gastric mucosal lesions. As cimetidine and ranitidine, the agent accelerated chronic gastric ulcer healing. Quiditene has been allowed for clinical studies in Russia.

[The effect of antihistaminic preparations on the binding of labelled mepyramine, ketanserin and quinuclidinyl benzilate in the rat brain]. / Vliianie antigistaminnykh preparatov na sviazyvanie mechennykh mepiramina, ketanserina i khinuklidinilbenzilata v mozge krysy.

The effects of some antiallergic drugs on H1-histamine, 5-HT2-serotonin, and M-cholinoreceptors ligand binding in the rat brain were studied in vitro. Dimedrol, dimebon, and phencarol bonded to H1-receptors: IC50 were 76 +/- 10, 153 +/- 15, 320 +/- 60 nM, respectively. Diazoline and dimebon had some affinity for 5-HT2-receptors, its IC50 was 880 +/- 90 nM. Dimedrol, phencarol and diazoline were found to be active against M-cholinoceptors, but when given in the maximal concentration (10 microM) it acted nonspecifically. In contrast to the other drugs, bicarphen had no effects on the binding of [3H]-mepyramine, [3H]-ketanserine, and [3H]-quinuclidinyl benzylate in the rat brain.

[The effect of the new Soviet antihistamine and antiserotonin preparation bikarfen on the central nervous system]. / Vliianie novogo otechestvennogo protivogistaminnogo i antiserotoninovogo preparata bikarfena na tsentral'nuiu nervnuiu sistemu.

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).

[Clinico-immunologic evaluation of the efficacy of bikarfen in allergic dermatoses]. / Kliniko-immunologicheskaia otsenka éffektivnosti bikarfena pri allergicheskikh dermatozakh.

It was found that the new native antihistamine and antiserotonin drug bicarphen possesses in patients with allergic dermatoses (eczema and neurodermatitis) more active antihistaminic, anti-inflammatory, antipruritic and antiallergic properties than commonly used drugs, particularly in cases with prevalence of exudative and allergic reactions of the immediate type. Normalization of rosette-forming T-lymphocytes and A and G immunoglobulins was essential.

[The effect of antihistamine preparations on the contraction of the isolated guinea pig ureter]. / Vliianie protivogistamininnykh preparatov na sokrashcheniia izolirovannogo mochetochnika morskoi svinki.

The effect of antihistaminics on contractions of the isolated guinea pig ureter was studied. The ureter contractions induced by histamine were prevented by H1-blockers: pipolphen (promethazine), dimedrol (diphenhydramine), phencarol (quifenadine), suprastin (chloropyramine), cyproheptadine and H2-blockers: cimetidine, ranitidine. Electric stimulation-induced contractions were prevented by suprastin. Phencarol, tavegil, cimetidine, ranitidine didn't act on the contractions. The electrically induced contractions were potentiated by pipolphen, dimedrol, cyproheptadine.

[Effect of prazosin on human prostatic adenoma tissue]. / Vliianie prazozina na tkan' adenomy predstatel'noi zhelezy cheloveka.

The effect of prazosin on epinephrine-induced contractions of human benign prostatic hyperplasia strips was studied. It was shown that prazosin has a pronounced adrenoblocking activity (EC50 = 5.10(-9) g/ml) but fails to affect strip contractions induced by KCL. It is suggested that prazosin can be used in the treatment of patients suffering from benign prostatic hyperplasia.

[Effect of antihistaminic preparations on gastric secretion in rats]. / Vliianie protivogistaminnykh preparatov na zheludochnuiu sekretsiiu y krys.

Experiments were made to study the influence of a new antihistaminic drug phencarol [(quinuclidyl-3) diphenylcarbinol hydrochloride] on gastric secretion in rats. Unlike the blockers of H1-histamine receptors (diphenhydramine, omeril, pyrilamine, and cyproheptadine), phencarol reduces secretion and the content of free hydrochloric acid in the gastric contents. The antacid activity of the drug is similar to that of the H2-receptor blocker, cimetidine. However, phencarol differs from the latter drug in the mechanism of action. The antacid action of phencarol is likely to be the result of its activation effect on diamine oxidase, which leads to a decrease in the content of active histamine in the tissues and diminution of its supply to H2-histamine receptors that control gastric secretion.

Modification of the activity of mitochondrial monoamine oxidases in vitro and in vivo.

Treatment of bovine brain mitochondrial membranes with iproniazid (Ip) (1 mM, 15 min) inhibited monoamine oxidase (MAO) activity (substrates: 5-hydroxytryptamine, tyramine, dopamine) and significantly (about 7-fold) increased histamine deaminating activity (HDA). A selective inhibitor of MAO-A clorgyline (contrary to deprenyl) prevented the increase in HDA. Ip (200 mg/kg; within 10-16 h after parenteral administration) markedly (about 6-fold) increased the level of the HDA) in brain mitochondria of mice and guinea pigs. At the same time, a decrease in content of histamine (Hi) and increase in content of 5-hydroxytryptamine was noted in the brains of mice. In anesthetized and non-anesthetized guinea pigs Ip decreased (or prevented) the bronchoconstriction and toxic effects caused by Hi. The antihistamine effects of Ip are apparently due to its being able to induce reversible qualitative alteration (transformation) of the catalytic activity of the membrane-bound MAO of type A, which acquires as a result of this transformation potent HDA.

[Effect of new antihistaminic preparations on the body's immunologic reactivity]. / Vliianie novykh protivogistaminovykh preparatov na immunologicheskuiu reaktivnost' organizma.

The effect of new antihistaminic drugs, phencarol and bicarphen, on immunologic reactivity of experimental animals was studied in comparison with diphenhydramine. Phencarol and bicarphen inhibited the delayed type allergic reactions to a greater degree than diphenydramine. Unlike diphenhydramine, phencarol and bicarphen injected simultaneously with test-antigen markedly decreased the number of rosette-forming lymphocytes in the immunocompetent organs (spleen, thymus, lymph nodes). Phencarol, bicarphen and diphenhydramine produced the same inhibitory effect on the content of antibody-producing cells in the spleen of mice.

[Effect of the antihistamine preparation, phencarol, on the central nervous system]. / Vliianie protivogistaminnogo preparata fenkarola na tsentral'nuiu nervunuiu sistemu.

The new antihistaminic and antiallergic drug phencarol (quinuclidy-3-diphenylcarbinol hydrochloride) in contradistinction to dimedrol (diphenhydramine) and diprazine (promethazin) exerts no pronounced depressant effect on the central nervous system. It does not significantly influence the period of action of hypnotic drugs, the effects produced by alcohol, spontaneous motor activity, summation capacity of the central nervous system, conditioned reflexes or electroencephalogram. That phencarol possesses no marked central action may be accounted for by its low lipophilic activity and little permeability of the blood brain barrier by this drug.

[Effect of the antihistamine preparation, fencarol, and other quinuclidyldiarylcarbinols on tissue aminoxidase activity]. / Vliianie protivogistaminnogo preparata fenkarola i drugikh khinuklidildiarilkarbinoov ba aktivnost' tkanevykh aminoksidaz.

In experiments in vivo, the derivatives of quinuclidylarylcarbinol, possessing an antihistaminic activity, fencarol, its di(o-tolyl)- and di(o-methoxyphenyl)-derivatives activate histamine oxidative deamination by diaminoxidase of the rat lungs and increase the histamine tissue level. Quinuclidyl-3-dithienyl carbinol inhibits the activity of diaminoxidase, but decreases the histamine tissue level. On the contrary, dimedrol (diphenhydramine), pipolfen (promethazin), pyrilamine and cyproheptadin exerted no effect on the activity of diaminoxidase or the histamine tissue level. All the compounds studied did not alter oxidative deamination of the rat brain serotonin by monoamine oxidase or the serotonin content in brain tissues.

[Inhibition of non-cytotoxic histamine liberation from isolated rat mast cells by antihistaminic preparations]. / Tormozhenie antigistaminnymi preparatami netsitotoksicheskogo vysvobozhdeniia gistamina iz izolirovannykh tuchnykh kletok krys.

Phenothiazines (chlorpromazine and promethazine) and antihistaminic quinuclidine derivatives [phencarol, quinuclidyl-3-di-(o-tolyl) carbinol, hydrochloride quinuclidyl-3-di-(o-methoxyphenyl) carbinol--HQMC] at concentrations preceding the histamine-releasing ones inhibited the compound 48/80-induced histamine release from the isolated rat mast cells. HQMC inhibited histamine release induced by selective liberators (compound 48/80, MCD-peptide, specific antigen), but potentiated histamine release induced by nonselective liberators (chlorpromazine, tryton X-100). The inhibition by HQMC of histamine release induced by compound 48/80 increased during 1 min and was reversible. The inhibitory effect of all the compounds tested was partially counteracted by glucose.

[Pharmacokinetics of the new Soviet, tritium-labelled, antihistamine preparation, phencarol]. / Farmakokinetika novogo otechestvennogo protivogistaminnogo preparata fenkarola, mechennogo tritiem.

As evidenced no less than 45 per cent of tritium-labelled antihistaminic drug phencarol (quinuclidine-3-diphenylcarbinol hydrochloride) introduced intragastrically to rats is absorbed. The maximal radioactivity in various organs is reached in 1--3 hours, with high specific radioactivity being recorded in the lungs and liver and low--in the brain. The drug or radioactive products of its tranformation are eliminated largely via the gastrointestinal tract and kidneys.