piperidines and pipethiaden

Topics: Analgesics; Animals; Binding, Competitive; Brain; Male; Migraine Disorders; Piperidines; Pizotyline; Rats; Rats, Inbred Strains; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Thiophenes

Pipethiadene, a prophylactic of vasomotoric headaches of the series of 4,9-dihydrothieno(2,3-c)-2-benzothiepine derivatives, shows a peripheralpharmacological profile of an antiallergic agent. The experiments in rats showed a high antianaphylactic effect of pipethiadene in the passive cutaneous anaphylaxis (PCA) test. Pipethiadene also exerted intensive antianaphylactoid action in rats on the liberator of histamine, compound 48/80, on dextran, and in the use of a combination of ovalbumin with indomethacin. In comparative pharmacological experiments with pizotifen and cyproheptadine an attempt was made to estimate the relative role of histamine and 5-hydroxytryptamine 5-HT) mediators in the employed experimental procedures in rats.

Topics: Anaphylaxis; Animals; Cyproheptadine; Female; Guinea Pigs; Mice; Migraine Disorders; Passive Cutaneous Anaphylaxis; Piperidines; Pizotyline; Rats

Drugs of the pizotifen type (pizotifen, cyproheptadine), possessing high H1-antihistamine and high antiserotonin activities in animal experiments, exert potent inhibitory actions on the passive cutaneous anaphylaxis (PCA) reaction in the rat. The drug pipethiadene, a 4,9-dihydrothieno(2,3-c)-2-benzothiepin derivative also belongs to this group. Selective histamine H1-antagonists alone are unable to cause pronounced reduction of the intensity of the PCA reaction in the rat, but in local reactions induced in rats by compound 48/80, histamine H1-receptors seem to play major role.

Topics: Animals; Cyproheptadine; Female; Histamine Antagonists; p-Methoxy-N-methylphenethylamine; Passive Cutaneous Anaphylaxis; Piperidines; Pizotyline; Rats; Rats, Inbred Strains; Serotonin Antagonists

The teratogenic and cytogenetic effects of two drugs with antihistamine properties, Pipethiadene and Pizotifen maleate, were investigated. Three groups of pregnant mice were treated daily with oral doses (0.24, 0.6 and 1.2 mg/kg) of these drugs from day 4 to day 16 of gestation. The following parameters were investigated: reproductive health of the dams, external, skeletal and visceral malformations of fetuses and frequencies of micronuclei and chromosome aberrations in bone marrow cells of dams. Oral administration of Pipethiadene or Pizotifen maleate produced no teratogenic effects. No elevation was observed in the frequencies of micronuclei and chromosome aberrations. However, the significant reduction of fetal weight after all doses of Pipethiadene or Pizotifen maleate was found to correlate well with the decreased values of the mitotic indices of bone marrow cells of mice, suggesting a potential embryotoxic effect of the tested substances.

Topics: Animals; Body Weight; Bone Marrow; Chromosome Aberrations; Female; Fetus; Histamine Antagonists; Mice; Piperidines; Pizotyline; Pregnancy; Teratogens

Tritium labelled anti-migraine drug 4-(1-methyl-4-piperidyliden)-4,9-dihydrothieno[2,3-c]-2-b enzothiepine (pipethiaden) was prepared. After oral and intravenous administration to rats not only the courses of total radioactivity in plasma and various organs were determined, but by means of TLC-radiometry also the levels of pipethiaden itself. After the oral dose 1.35 mg/kg the plasma levels of pipethiaden did not exceed 3.5 ng/ml. Some pharmacokinetic parameters (e.g. t1/2 el-4 h) were calculated by compartmental analysis of plasma levels.

Topics: Administration, Oral; Animals; Biotransformation; Injections, Intravenous; Kinetics; Male; Models, Biological; Piperidines; Rats; Rats, Inbred Strains; Tissue Distribution