Derivatives of 3,4-dihydrocarbostyril as .beta.-adrenergic blocking agents

Nakagawa, Kazuyuki; MURAKAMI, NANAMI; Yoshizaki, Shiro; Tominaga, Michiaki; Mori, Hideo; Yabuuchi, Youichi; Shintani, Shigeyuki

doi:10.1021/jm00251a013

Cited by 50 publications

(14 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From these findings, they proposed that adrenaline is taken up, stored, released as a co-transmitter with noradrenaline, and then activates prejunctional fiadrenoceptors. We have shown that carteolol, a nonselective fl-adrenoceptor antagonist (Nakagawa et al, 1974), readily and stereoselectively inhibits the evoked release of noradrenaline from guinea-pig pulmonary arteries in the absence of any agents (Kuwahara et al, 1986). In Amersham/Searle, U.S.A.) and ascorbic acid 100mg I -as described previously (Misu et al, 1981;1983 Injections of DOCA 0.2 mg per animal day-' plus hydrocortisone 1.0mg per animal day-' for 4 days to adrenalectomized guinea-pigs, before the isolation of pulmonary arteries, did not modify the spontaneous and evoked 3H-release at SI, compared to the equivalent release obtained in arteries from adrenalectomized animals (Tables 1, 3 and 4).…”

Section: Introductionmentioning

confidence: 99%

Evidence for tonic activation of prejunctional β‐adrenoceptors in guinea‐pig pulmonary arteries by adrenaline derived from the adrenal medulla

Misu

Kuwahara

Amano

et al. 1989

British J Pharmacology

View full text Add to dashboard Cite

1 The effects of ( ± )-carteolol 10 8 M to 10-6 M, a non-selective fl-antagonist, applied cumulatively, on stimulation-evoked 3H-release at 1 Hz were studied in pulmonary arteries isolated from guineapigs. The guinea-pigs were subjected to either bilateral adrenalectomy, adrenalectomy followed by injections of deoxycorticosterone acetate (DOCA) and hydrocortisone, bilateral adrenodemedullation or a sham operation, and then loaded in vitro with [3H]-noradrenaline. 2 Carteolol inhibited 3H-output in arteries from sham-operated animals in a concentrationdependent manner. This inhibitory effect was not found in pulmonary arteries from animals subjected to adrenalectomy or adrenodemedullation. However, DOCA and hydrocortisone pretreatment, did not prevent the disappearance of the carteolol-induced inhibition of 3H-release. 3 Adrenalectomy and adrenodemedullation depleted or markedly reduced the endogenous contents of adrenaline in pulmonary arteries without altering the levels of dopamine and noradrenaline. 4 It is concluded that adrenaline, mainly derived from the adrenal medulla, acts as an endogenous agonist for tonically functioning prejunctional fl-adrenoceptors in guinea-pig pulmonary arteries, probably by being taken up and co-released with noradrenaline.

show abstract

Section: Introductionmentioning

confidence: 99%

Evidence for tonic activation of prejunctional β‐adrenoceptors in guinea‐pig pulmonary arteries by adrenaline derived from the adrenal medulla

Misu

Kuwahara

Amano

et al. 1989

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Concerning the potency of f3-adrenoreceptor blockers, carteolol is about ten times as potent as propranolol (Nakagawa et al 1974) and Indenolol (Tachikawa and Takenaka 1973). Other non-specific /3-adrenoreceptor blockers, oxprenolol (Jones et al 1981) and sotalol (Wahlberg et al 1976), which had been reported to be ineffective on the serum levels of thyroid hormones, were less potent than propranolol (Frishman 1979).…”

Section: Discussionmentioning

confidence: 99%

“…We studied the effect of two non-selective /3-adrenoreceptor blockers ; carteolol with strong intrinsic sympathomimetic activity (ISA) and no membrane stabilizing activity (MSA) (Nakagawa et al 1974) and indenolol with MSA and weak ISA (Tachikawa and Takenaka 1973), and one /31-selective adrenoreceptor blocker, metoprolol without ISA and MSA (Frishman 1981), on the heart rate and serum thyroid hormones in patients of hyperthyroidism.…”

mentioning

confidence: 99%

Effect of carteolol, indenolol and metoprolol on the thyroid hormone of hyperthyroid patients.

Yamamoto

Sato

Yoshida

et al. 1985

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

----Thirty-four hyperthyroid patients were divided into four groups : placebo, carteolol (20 mg/day), indenolol (60 mg/day) and metoprolol (120 mg/day) groups. The heart rate was determined before and two weeks after the treatment with each drug. Serum levels of T4, T3 and rT3 were measured before, and one and two weeks after the treatment. Both indenolol and metoprolol significantly reduced the heart rate (p <0.01 and p <0.05, respectively), whereas carteolol was ineffective. Carteolol significantly decreased T4 from 23.4± 4.4 ,u g/ 100 ml to 20.1 + 3.2,u g/ 100 ml (p < 0.01) in one week and to 20.0±3.7,ug/100 ml (p <0.01) in two weeks. T3 and rT3 were also decreased significantly (p <0.05 and p <0.01, respectively) two weeks after the treatment with carteolol. After two weeks of indenolol treatment, T4 was decreased significantly from 26.2±8.5 u g/ 100 ml to 23.9±8.2 p g/100 ml (p < 0.05) and T3 from 789+391ng/100 ml to 592+340 ng/100 ml (p <0.02). Metoprolol had no effect on serum thyroid hormone levels. The decrease in the serum level of thyroid hormones by carteolol and indenolol but not by metoprolol in patients with hyperthyroidism would be due to the blockade of f2-adrenoreceptors concerning with thyroid hormone secretion.carteolol; indenolol ; metoprolol ; thyroid hormone ; hyperthyroidism Propranolol causes a fall in serum triiodothyronine (T3) concentration in hyperthyroid patients (Verhoeven et al. 1977 ;Kallner et al. 1978 ;Saunders et al. 1978), probably by its action on peripheral conversion of thyroxine (T4) to T3 and reverse T3 (rT3) (Heyma et al. 1980;Nilsson et al. 1980), although f3-adrenoreceptor blockers other than propranolol were reported to have no effect on serum thyroid hormones (Murchison et al. 1976;Wahlberg et al. 1976;Nilsson et al. 1979: Jones et al. 1981.

show abstract

“…It has been reported that a newly synthesized beta-blocker, carteolol (dl-5(3-tert-butylamino 2-hydroxy) proxy-3,4-dihydrocarbostyril hydrochloride), is 10-30 times more potent than propranolol, and in higher doses has sympathomimetic properties (1)(2)(3). In the present study, the sympathomimetic effects of carteolol on heart rate and contractility were in vestigated, using the isolated, blood-perfused clog atrium preparation (4,5 Vertical lines indicate SEM.…”

Section: Do and Pindolol Or Propranololmentioning

confidence: 99%

Differential Inotropic-Chronotropic Action of Carteolol

Chiba

1977

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

Derivatives of 3,4-dihydrocarbostyril as .beta.-adrenergic blocking agents

Cited by 50 publications

References 3 publications

Evidence for tonic activation of prejunctional β‐adrenoceptors in guinea‐pig pulmonary arteries by adrenaline derived from the adrenal medulla

Evidence for tonic activation of prejunctional β‐adrenoceptors in guinea‐pig pulmonary arteries by adrenaline derived from the adrenal medulla

Effect of carteolol, indenolol and metoprolol on the thyroid hormone of hyperthyroid patients.

Differential Inotropic-Chronotropic Action of Carteolol

Contact Info

Product

Resources

About