Nonstereoselective aspects of propranolol pharmacodynamics

1986 ◽  
Vol 64 (12) ◽  
pp. 1455-1462 ◽  
Author(s):  
M. Alkondon ◽  
A. Ray ◽  
P. Sen
Keyword(s):  
Inhibitory Action ◽  
Blocking Agent ◽  
Inhibitory Effect ◽  
The Body ◽  
Cholinergic Mechanism ◽  
Central Effects ◽  
Biochemical Studies ◽  
Β Blockers ◽  
Adrenergic Blocking ◽  
Therapeutic Profile

Twenty years after its discovery, the β-adrenergic blocking agent propranolol continues to interest pharmacologists and clinicians. Its therapeutic profile has extended to areas beyond the purview of the cardiovascular system, and its ocular and central nervous system effects have been well documented. In addition, it still remains a very good pharmacological tool to map out the adrenergic β-receptors in the body, and stereoisomers of propranolol and other β-blockers serve as valuable agents to distinguish between the effects related to β-adrenoceptors and those which are not. The primary purpose of this review is to summarize the evidence indicating that β-adrenergic blocking agents lack stereoselectivity in some of their effects, including several of considerable therapeutic importance. Because many pharmacological actions of propranolol followed a nonsteroselective pattern, the involvement of β-adrenoceptors in them was questioned and this led to the search for alternate mechanisms to explain these effects. Studies with propranolol and some related drugs indicated the involvement of a cholinergic mechanism in their antiarrhythmic, ocular hypotensive and some central effects. Also, a presynaptic inhibitory effect at the skeletal neuromuscular junction has been suggested to explain the benefical effect of propranolol and other β-blockers in tremor. Biochemical studies with these drugs revealed their inhibitory action on the cholinesterase enzyme in blood and other tissues like myocardium and brain. It is thus hypothesized that modulation of cholinergic neurotransmission by propranolol could explain some of its nonstereoselective actions and open new vistas in propranolol pharmacodynamics.

ADRENERGIC CONTROL MECHANISM FOR ACTH SECRETION IN MAN

1973 ◽  
Vol 74 (2) ◽  
pp. 263-270 ◽  
Author(s):  
Yoshikatsu Nakai ◽  
Hiroo Imura ◽  
Teruya Yoshimi ◽  
Shigeru Matsukura
Keyword(s):  
Intravenous Infusion ◽  
Human Subjects ◽  
Blocking Agent ◽  
Inhibitory Effect ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Glucose Levels ◽  
Alpha Receptors ◽  
Normal Human ◽  
Adrenergic Blocking

ABSTRACT In order to determine if an adrenergic mechanism is involved in the secretion of corticotrophin (ACTH), the effect of adrenergic-blocking or -stimulating agent on plasma ACTH, cortisol and glucose levels was studied in normal human subjects. The intravenous infusion of methoxamine, an alpha adrenergic-stimulating agent, caused a rise in plasma ACTH and cortisol. This increase in plasma ACTH and cortisol was significantly inhibited by the simultaneous administration of phentolamine, an alpha adrenergic-blocking agent, in combination with methoxamine. The intravenous infusion of propranolol, a beta adrenergic-blocking agent, caused no significant change in plasma ACTH and cortisol, although it enhanced the plasma ACTH response to insulin-induced hypoglycaemia. On the other hand, alpha adrenergicblockade by intravenous infusion of phentolamine significantly suppressed the plasma ACTH response to insulin-induced hypoglycaemia. These studies suggest a stimulatory effect of alpha receptors and a possible inhibitory effect of beta receptors on ACTH secretion in man.

The central effects of the β-adrenergic blocking agent INPEA

1972 ◽  
Vol 11 (5) ◽  
pp. 609-614 ◽  
Author(s):  
R.Yu. Ilyutchenok ◽  
M.A. Gilinsky ◽  
A.G. Yeliseyeva ◽  
B.P. Jivotikoff ◽  
L.V. Loskutova ◽  
...  
Keyword(s):  
Blocking Agent ◽  
Central Effects ◽  
Adrenergic Blocking

Inhibition of ADP-Induced Responses in Human Platelets by Agents Elevating the Cyclic AMP Level: Comparison of Aggregation and Shape Change

1984 ◽  
Vol 52 (03) ◽  
pp. 333-335 ◽  
Author(s):  
Vider M Steen ◽  
Holm Holmsen
Keyword(s):  
Inhibitory Action ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Shape Change ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Inhibitory Effects ◽  
Early Step ◽  
Stimulus Response ◽  
Sequential Relationship

SummaryThe inhibitory effect of cAMP-elevating agents on shape change and aggregation in human platelets was studied to improve the understanding of the sequential relationship between these two responses.Human platelet-rich plasma was preincubated for 2 min at 37° C with prostaglandin E1 or adenosine, agents known to elevate the intracellular level of cAMP. Their inhibitory effects on ADP-induced shape change and aggregation were determined both separately and simultaneously. The dose-inhibition patterns for shape change and aggregation were similar for both PGE1 and adenosine. There was no distinct difference between the inhibitory action of these two inhibitors.These observations suggest that elevation of the intracellular concentration of cAMP interferes with an early step in the stimulus-response coupling that is common for aggregation and shape change.

Contribution of Adrenaline to the Fibrinolytic Activity Evoked by E. Coli Endotoxin in the Rat

1983 ◽  
Vol 50 (02) ◽  
pp. 557-559 ◽  
Author(s):  
J F Fracasso ◽  
A M Rothschild
Keyword(s):  
Fatty Acid ◽  
Adrenal Gland ◽  
Intravenous Injection ◽  
Fibrinolytic Activity ◽  
Blocking Agent ◽  
E Coli ◽  
Adrenergic Blocking

SummaryIntravenous injection of E. coli endotoxin (ETX), of adrenaline (AD) or of carbamylcholine (CBCH), caused fibrinolytic activity (FA), directly detectable on plasminogen-rich fibrin plates, to appear in the plasma of the rat. Adrenodemedul- lation abolished responses to ETX or CBCH, but enhanced those to AD. Rats given ETX exhibited marked hypotension, followed by a compensatory phase of normotension abolished by adrenodemedullation and significantly attenuated by phenoxy- benzamine, an a-adrenergic blocking agent which however failed to block FA caused by either ETX or AD. Aspirin, but not indomethacin, inhibited FA evoked by ETX, AD or CBCH. These results suggest that FA evoked by ETX in the rat is caused by AD released from the adrenal gland and does involve the fatty acid cyclooxygenase system.

Mechanism of the Antiplatelet Action of Dipyridamole in Whole Blood: Modulation of Adenosine Concentration and Activity

1986 ◽  
Vol 55 (01) ◽  
pp. 012-018 ◽  
Author(s):  
Paolo Gresele ◽  
Jef Arnout ◽  
Hans Deckmyn ◽  
Jos Vermylen
Keyword(s):  
Platelet Aggregation ◽  
Adenosine Receptor ◽  
Whole Blood ◽  
Blood Cells ◽  
Inhibitory Action ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Adenosine Concentration ◽  
Pharmacological Studies

SummaryDipyridamole inhibits platelet aggregation in whole blood at lower concentrations than in plasma. The blood cells responsible for increased effectiveness in blood are the erythrocytes. Using the impedance aggregometer we have carried out a series of pharmacological studies in vitro to elucidate the mechanism of action of dipyridamole in whole blood. Adenosine deaminase, an enzyme breaking down adenosine, reverses the inhibitory action of dipyridamole. Two different adenosine receptor antagonists, 5’-deoxy-5’-methylthioadenosine and theophylline, also partially neutralize the activity of dipyridamole in blood. Enprofylline, a phosphodiesterase inhibitor with almost no adenosine receptor antagonistic properties, potentiates the inhibition of platelet aggregation by dipyridamole. An inhibitory effect similar to that of dipyridamole can be obtained combining a pure adenosine uptake inhibitor (RE 102 BS) with a pure phosphodiesterase inhibitor (MX-MB 82 or enprofylline). Mixing the blood during preincubation with dipyridamole increases the degree of inhibition. Lowering the haematocrit slightly reduces the effectiveness.Although we did not carry out direct measurements of adenosine levels, the results of our pharmacological studies clearly show that dipyridamole inhibits platelet aggregation in whole blood by blocking the reuptake of adenosine formed from precursors released by red blood cells following microtrauma. Its slight phosphodiesterase inhibitory action potentiates the effects of adenosine on platelets.

Inhibition of Yeast Growth by Tryptamine and Recovery with Tryptophan

2020 ◽  
Vol 16 (1) ◽  
pp. 48-52 ◽  
Author(s):  
Chandrika Kadkol ◽  
Ian Macreadie
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Carbon Source ◽  
Competitive Inhibition ◽  
Yeast Species ◽  
Inhibitory Effect ◽  
The Body ◽  
Inhibitory Effects ◽  
Trna Synthetases ◽  
Fermentative Growth ◽  
Biogenic Monoamine

Background: Tryptamine, a biogenic monoamine that is present in trace levels in the mammalian central nervous system, has probable roles as a neurotransmitter and/or a neuromodulator and may be associated with various neuropsychiatric disorders. One of the ways tryptamine may affect the body is by the competitive inhibition of the attachment of tryptophan to tryptophanyl tRNA synthetases. Methods: This study has explored the effects of tryptamine on growth of six yeast species (Saccharomyces cerevisiae, Candida glabrata, C. krusei, C. dubliniensis, C. tropicalis and C. lusitaniae) in media with glucose or ethanol as the carbon source, as well as recovery of growth inhibition by the addition of tryptophan. Results: Tryptamine was found to have an inhibitory effect on respiratory growth of all yeast species when grown with ethanol as the carbon source. Tryptamine also inhibited fermentative growth of Saccharomyces cerevisiae, C. krusei and C. tropicalis with glucose as the carbon source. In most cases the inhibitory effects were reduced by added tryptophan. Conclusion: The results obtained in this study are consistent with tryptamine competing with tryptophan to bind mitochondrial and cytoplasmic tryptophanyl tRNA synthetases in yeast: effects on mitochondrial and cytoplasmic protein synthesis can be studied as a function of growth with glucose or ethanol as a carbon source. Of the yeast species tested, there is variation in the sensitivity to tryptamine and the rescue by tryptophan. The current study suggests appropriate yeast strains and approaches for further studies.

POSSIBLE ROLE OF 5α-ANDROSTANE-3α,17β-DIOL IN THE CONTROL OF FOLLICLE-STIMULATING HORMONE SECRETION IN THE IMMATURE FEMALE RAT

1982 ◽  
Vol 92 (1) ◽  
pp. 37-42 ◽  
Author(s):  
H. M. A. MEIJS-ROELOFS ◽  
P. KRAMER ◽  
L. GRIBLING-HEGGE
Keyword(s):  
Inhibitory Action ◽  
Combined Treatment ◽  
Hormone Secretion ◽  
Inhibitory Effect ◽  
Ovariectomized Rats ◽  
Female Rat ◽  
Immature Rat ◽  
Rat Strain ◽  
Intact Rats

A possible role of 5α-androstane-3α,17β-diol (3α-androstanediol) in the control of FSH secretion was studied at various ages in ovariectomized rats. In the rat strain used, vaginal opening, coincident with first ovulation, generally occurs between 37 and 42 days of age. If 3α-androstanediol alone was given as an ovarian substitute, an inhibitory effect on FSH release was evident with all three doses tested (50, 100, 300 μg/100 g body wt) between 13 and 30 days of age; at 33–35 days of age only the 300 μg dose caused some inhibition of FSH release. Results were more complex if 3α-androstanediol was given in combined treatment with oestradiol and progesterone. Given with progesterone, 3α-androstanediol showed a synergistic inhibitory action on FSH release between 20 and 30 days of age. However, when 3α-androstanediol was combined with oestradiol a clear decrease in effect, as compared to the effect of oestradiol alone, was found between 20 and 30 days of age. Also the effect of combined oestradiol and progesterone treatment was greater than the effect of combined treatment with oestradiol, progesterone and 3α-androstanediol. At all ages after day 20 none of the steroid combinations tested was capable of maintaining FSH levels in ovariectomized rats similar to those in intact rats. It is concluded that 3α-androstanediol might play a role in the control of FSH secretion in the immature rat, but after day 20 the potentially inhibitory action of 3α-androstanediol on FSH secretion is limited in the presence of oestradiol.

Sign in / Sign up

Export Citation Format

Share Document