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Antiallergic effect and its mechanism of tetrandrine
227
pharmacokinetic parameters were examined in guinea pig. The absorption rates of a-Terpineol by aerosol inhalation and oral administration were rapid. The drug was distributed widely in vivo. It was found in tracheal smooth muscle, lung, heart, liver and kidney with rather high concentrations. The elimination rate of a-Terpineol was fast, its biological half-lives were 5.92 and 8.45 hours for inhalation and oral administration, respectively. a-Terpineol mainly excreted in urine as unchanged form. a-Terpineol were given by aerosol to treat 400 cases of bronchial asthma FEV, and MMEF were increased after treatment. Total effectiveness was 98% of cases. It had very low frequency of increase in heart rate. I P.mo.017 I
Antiallergic effect and its mechanism of te
e
Bian, R.-L. Institute of Clinical Pharmacology, Zhejiang Medical University, People’s Republic of China
Tetrandrine (5 mg/kg and 30 mg/kg, i.v.; 100 mg/kg and 300 mg/kg, i.g.) inhibited passive cutaneous anaphylaxis, reversed cutaneous anaphylaxis of rats, Forssman cutanous vasculitis reaction of guinea pigs, Arthus reaction of rabbits, foot pod delayed anaphylaxis of mice induced by red blood cells of sheep and contact dermatitis induced by dinitrofluorobenzene, respectively. It also inhibited Schultz-Dale reaction of Ileum tracheal smooth muscle and lung strip of guinea pigs at 3-15 pg/rnl concentration. IC,, for histamine and acetylcholine were 50 ag/ml and 66 pg/ml on the ileum of guinea pigs, respectively. IC,, for SRS-A was 6-6.6 pg/ml on the tracheal and lung strip of guinea pig. Tetrandrine (0.25 nM) provented the degranulation of rat peritoneal mast cells induced by antigen (redix trichosanthis; 10 as/ml), ionophore calcimycin (A23187,lSO nM) or compound 48/80 1 pg,/ml under transmission and scanning electron microscopes, and inhibited the release of histamine from mast cells induced by antigen or dextran. The cyclooxygenase of sheep vesicular glands and lipoxygenase of pig leukocytes were inhibited by 0.25 mM tetrandrine. Tetrandrine (0.25 mM) suppressed the 45Ca influx via the histamine-opened channel and the high K-opened channel in dog and guinea pig tracheal smooth muscle Tetrandrine (32 pM or 65 PM) inhibited the increase by calcimycin (25 PM), leukotriene B4 (60 CM) platelet activating factor (10 PM) of intracellular Ca in rat neutrophils exposed to Hank’s solution containing Ca.
1P.mo.018 1
Effect of WAL-
1, a new antiallergic drug, on the bronchoconstrictions irbguinea pigs
iator-in
Kanai, Y. and Misawa, M. Department of Applied Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebaro, Shinagawa-ku, Tokyo 142. Japan
WAL-801 (3-amino-9,13b-dihydro-lH-dibenz-(c,f)imidazo(lJ-a)azepine hydrochloride) is a new antiallergic drug with HI-receptor blocking activity, devoid of central depression such as sedation and drowsiness. WAl-801 is known to inhibit the release of chemical mediators from mast cells. In the present study, the effects of WAL-801 on the bronchoconstrictor actions of chemical mediators probably playing a role in bronchial asthma, such as histamine, substance P, bradykinin and U-46619, a thromboxane AZ mimetic, were studied in comparison with those of other antiallergic drugs, such as ketotifen, azelastine and oxatomide. Male Hartley guinea pigs (250-420 g) were orally administered the antiallergic drugs 1 hr before i.v. administrations of the above chemical mediators. Water (vs. WAL-801, ketotifen and azelastine) and 0.3% CMC-Na (vs. oxatomide) were given to the control groups. The animals anesthetized with pentobarbital-Na (48 rng/-kg, i.p.), were immobilized with decamethonium bromide (2 mg/kg, i.v.) and ventilated artificially through a tracheal cannula at a frequency of
pharmacokinetic parameters were examined in guinea pig. The absorption rates of a-Terpineol by aerosol inhalation and oral administration were rapid. The drug was distributed widely in vivo. It was found in tracheal smooth muscle, lung, heart, liver and kidney with rather high concentrations. The elimination rate of a-Terpineol was fast, its biological half-lives were 5.92 and 8.45 hours for inhalation and oral administration, respectively. a-Terpineol mainly excreted in urine as unchanged form. a-Terpineol were given by aerosol to treat 400 cases of bronchial asthma FEV, and MMEF were increased after treatment. Total effectiveness was 98% of cases. It had very low frequency of increase in heart rate. I P.mo.017 I
Antiallergic effect and its mechanism of te
e
Bian, R.-L. Institute of Clinical Pharmacology, Zhejiang Medical University, People’s Republic of China
Tetrandrine (5 mg/kg and 30 mg/kg, i.v.; 100 mg/kg and 300 mg/kg, i.g.) inhibited passive cutaneous anaphylaxis, reversed cutaneous anaphylaxis of rats, Forssman cutanous vasculitis reaction of guinea pigs, Arthus reaction of rabbits, foot pod delayed anaphylaxis of mice induced by red blood cells of sheep and contact dermatitis induced by dinitrofluorobenzene, respectively. It also inhibited Schultz-Dale reaction of Ileum tracheal smooth muscle and lung strip of guinea pigs at 3-15 pg/rnl concentration. IC,, for histamine and acetylcholine were 50 ag/ml and 66 pg/ml on the ileum of guinea pigs, respectively. IC,, for SRS-A was 6-6.6 pg/ml on the tracheal and lung strip of guinea pig. Tetrandrine (0.25 nM) provented the degranulation of rat peritoneal mast cells induced by antigen (redix trichosanthis; 10 as/ml), ionophore calcimycin (A23187,lSO nM) or compound 48/80 1 pg,/ml under transmission and scanning electron microscopes, and inhibited the release of histamine from mast cells induced by antigen or dextran. The cyclooxygenase of sheep vesicular glands and lipoxygenase of pig leukocytes were inhibited by 0.25 mM tetrandrine. Tetrandrine (0.25 mM) suppressed the 45Ca influx via the histamine-opened channel and the high K-opened channel in dog and guinea pig tracheal smooth muscle Tetrandrine (32 pM or 65 PM) inhibited the increase by calcimycin (25 PM), leukotriene B4 (60 CM) platelet activating factor (10 PM) of intracellular Ca in rat neutrophils exposed to Hank’s solution containing Ca.
1P.mo.018 1
Effect of WAL-
1, a new antiallergic drug, on the bronchoconstrictions irbguinea pigs
iator-in
Kanai, Y. and Misawa, M. Department of Applied Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebaro, Shinagawa-ku, Tokyo 142. Japan
WAL-801 (3-amino-9,13b-dihydro-lH-dibenz-(c,f)imidazo(lJ-a)azepine hydrochloride) is a new antiallergic drug with HI-receptor blocking activity, devoid of central depression such as sedation and drowsiness. WAl-801 is known to inhibit the release of chemical mediators from mast cells. In the present study, the effects of WAL-801 on the bronchoconstrictor actions of chemical mediators probably playing a role in bronchial asthma, such as histamine, substance P, bradykinin and U-46619, a thromboxane AZ mimetic, were studied in comparison with those of other antiallergic drugs, such as ketotifen, azelastine and oxatomide. Male Hartley guinea pigs (250-420 g) were orally administered the antiallergic drugs 1 hr before i.v. administrations of the above chemical mediators. Water (vs. WAL-801, ketotifen and azelastine) and 0.3% CMC-Na (vs. oxatomide) were given to the control groups. The animals anesthetized with pentobarbital-Na (48 rng/-kg, i.p.), were immobilized with decamethonium bromide (2 mg/kg, i.v.) and ventilated artificially through a tracheal cannula at a frequency of