Antagonists at Muscarinic Cholinergic Receptors
Kenneth J. Broadley in Autonomic Pharmacology, 2017
The muscarinic receptor antagonists interact with the muscarinic receptors, produce no stimulant or agonist effects by themselves, but inhibit the effects of endogenously released Ach or exogenously introduced muscarinic agonists. The principal targets for antagonism are the postjunctional M2 and M3 muscarinic receptors on cardiac and smooth muscle and glandular tissues, which are normally activated by the release of Ach from postganglionic parasympathetic nerve terminals. Muscarinic receptors are distributed throughout the brain and, provided that the antagonist is capable of crossing the blood-brain barrier, the central effects upon mood, behaviour and cognitive powers with therapeutic doses are primarily due to antagonism of muscarinic receptors. The competitive tertiary amine class of muscarinic antagonists has been combined with the ß-haloalkylamine structure to produce irreversible muscarinic antagonists. The prototype antimuscarinic agent is atropine and a description of its pharmacology serves to illustrate the pharmacological effects of muscarinic blockade in general and remains relevant to the majority of therapeutically useful agents.
Cardiovascular Pharmacology Of Dopamine Receptor Agonists
M.D. Francesco Amenta in Peripheral Dopamine Pathophysiology, 2019
This chapter reviews some experimental evidence supporting the classification and distribution of cardiovascular dopamine (DA) receptors, discusses the cardiovascular and renal effects of DA receptor agonists, and addresses the involvement of second messenger systems in mediating some of the changes elicited following activation of specific DA receptors. The effect of DA and several DA analogs on renal blood flow was studied in detail, and the use of several different types of receptor antagonists led to the identification and characterization of a specific receptor for DA. Experiments performed in conscious rats show that selective DA2 receptor antagonists caused increases in plasma aldosterone, but DA1 receptor antagonists had no effect on plasma aldosterone. Several ergot compounds have been shown to possess agonistic action at dopamine receptors. In the presence of both DA1 and DA2 receptor antagonists, DA failed to produce any changes in cAMP.
Sympathomimetic Amines: Actions and Uses
Kenneth J. Broadley in Autonomic Pharmacology, 2017
This chapter covers the pharmacological actions and uses of agonists at the receptors: the sympathomimetic amines. The activity of a sympathomimetic at an organ or tissue is dependent upon the receptor type or types that are present and upon the selectivity and potency of the agonist for the receptor. The first indication that sympathomimetic amines could exert their effects by different pharmacological mechanisms was the observation that cocaine potentiated the effects of adrenaline but antagonized the effects of tyramine. The chapter discusses the structural requirements of sympathomimetic amines for direct and indirect activity. The pharmacological responses to sympathomimetic amines are generally the same as are the physiological responses to sympathetic nerve stimulation. Indirectly acting sympathomimetic amines exert their pharmacological response by release from sympathetic neurones of noradrenaline in active form so that it stimulates the α- and β-adrenoceptors.
Luteal phase support with GnRH agonist does not eliminate the risk for ovarian hyperstimulation syndrome
Published in Gynecological Endocrinology, 2019
This study aims to report a case of early, severe ovarian hyperstimulation syndrome (OHSS) following GnRH agonist trigger for final oocyte maturation despite luteal support with a GnRH agonist. Contrary to the claim that luteal support using a GnRH agonist eliminates the risk for OHSS in high-risk patients, this report alerts practitioners to the risk of severe OHSS development despite GnRH agonist luteal support in patients receiving GnRH antagonist protocol with GnRH agonist triggering and cautions the practitioners to consider other measures of OHSS prevention.
The principles of agonist pharmacotherapy for psychostimulant dependence
Published in Drug and Alcohol Review, 2008
Issues. Psychostimulant dependence is a chronic, relapsing condition which is highly treatment refractory. No medications to date have been any more successful than placebo in reducing psychostimulant use in dependent patients. Agonist strategies have attracted limited attention. Approach. Successful examples of agonist pharmacotherapy in the treatment of heroin and nicotine dependence are first considered. Agonist pharmacological approaches to the treatment of psychostimulant dependence are then examined, based on the dopamine receptor agonist and indirect dopamine agonist strategies. Finally, the potential extension of the concept of agonist pharmacotherapy to include the novel non-amphetamine-type stimulant, modafinil, is discussed. Conclusions. Agonist approaches appear to be viable with risks outweighed by benefits in carefully selected, monitored and motivated patients. On the other hand, the effectiveness of indirect agonists such as dexamphetamine and methylphenidate are not established. Further research is required to determine optimal treatment models (whether maintenance or withdrawal), effective safe dosages and duration (short or long term). [Shearer J. The principles of agonist pharmacotherapy for psychostimulant dependence. Drug Alcohol Rev 2008;27:301–308]
A global model to define the behavior of partial agonists (bell-shaped dose-response inducers) in pharmacological evaluation of activity in the presence of the full agonist
Published in Journal of Biopharmaceutical Statistics, 1998
Krishnendu Ghosh, Emily S. Shen, Brian J. Arey, Francisco J. López
The dose-response models for full agonists and for a particular type of partial agonist can be described by sigmoidal curves and bell-shaped curves, respectively. The methods currently used to evaluate the interaction of a full agonist and a partial agonist require a large number of experimental units and base their analysis on nonlinear regression analysis, which may not be statistically appropriate. We propose an appropriate design and a global nonlinear model to evaluate such interactions. The new model allows us to estimate the interaction parameters and the parameters that characterize the individual partial agonist curve and the full agonist curve.
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