Antagonistic actions

Give me a lever long enough, and a prop strong enough, and I can single-handedly move the world. 

FIGURE 6.20.5 Basic diagram of the cardiovascular controller. Innervation by sympathetic and parasympathetic nerves allows antagonistic actions. The many inputs to the controller are not shown. (From Johnson, A.T., Biomechanics and Exercise Physiology Quantitative Modeling, CRC Press/Taylor Francis, Boca Raton, FL, 2007. With permission.) 

The same cardiovascular control system regulates blood distribution and blood pressure by affecting the small arterioles of the peripheral blood vasculature. The entrance to each of these vessels is surrounded by a sphincter muscle (a ring of involuntary muscle that surrounds the arteriolar aperture) with sympathetic, and in some cases, parasympathetic, nerve fibers. The sphincter is usually contracted. When the signal comes for the muscle to relax, the neuron produces nitric oxide at the neuromuscular junction, and this gas relaxes the sphincter. When the sphincter muscle expands, it increases the area through which blood flows and decreases its resistance. With decreased resistance, blood pressure falls. 

There is a second penalty to this type of control it is slow. Passive exhalation cannot proceed any faster than allowed by the recoil pressure and airway resistance. Flow rate is exponential in shape, which means initially high and slowing with time (see Section 4.2.3), with a time constant given by the product of capacity (or compliance) and resistance of the system. 

Imprecise and slow control cannot be tolerated during the demands of exercise. Excess COj must be removed at a rate high enough that it doesn t poison the body. Exercise breathing control becomes active in both inhalation and exhalation directions. 

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Future Outlook for Antidepressants. Third-generation antidepressants are expected to combine superior efficacy and improved safety, but are unlikely to reduce the onset of therapeutic action in depressed patients (179). Many dmgs in clinical development as antidepressive agents focus on estabhshed properties such as inhibition of serotonin, dopamine, and/or noradrenaline reuptake, agonistic or antagonistic action at various serotonin receptor subtypes, presynaptic tt2-adrenoceptor antagonism, or specific monoamine—oxidase type A inhibition. Examples include buspirone (3) (only... 

IFN- 3 reduces the induction by inflammatory cytokines of adhesion molecules and of MHC class I and II complex on endothelial cells, a process preceding attachment and transendothelial migration of T-cells. These anti-inflammatory effects of IFN- 3 exemplify antagonistic actions of type I and type IIIFN. There is, indeed, much clinical evidence for the involvement of IFN-y in inflammatory processes - through activation of iNOS and subsequent secretion of NO - leading to the establishment of autoimmune diseases as for instance in rheumatoid arthritis. 

Naltrexone completely blocks the effects of IV opiates, as well as drugp with agonist-antagonist actions (butorphanol, nalbuphine, and pentazocine). The mechanism of action appears to be the same as that for naloxone... 

Turning now to chemical attack, many predators immobilize their prey by injecting toxins, often neurotoxins, into them. Examples include venomous snakes, spiders, and scorpions. Some spider toxins (Quick and Usherwood 1990 Figure 1.3) are neurotoxic through antagonistic action upon glutamate receptors. The venom of some scorpions contains polypeptide neurotoxins that bind to the sodium channel. 

ACh is released from the large non-spiny striatal interneurons (Fig. 15.10) which only represent some 5% of total striatal neuron number. Since ACh is excitatory and DA inhibitory on striatal neurons, various schemes have been proposed to balance their antagonistic action but the role of ACh in striatal function (and PD) appears to be relatively minor. 

Contreras, P. Rafferty, M. Jacobson, A. Rice, K. Quirion, R. and O Donohue, T. Agonist and antagonist actions of phencyclidine derivatives on PCP receptors and behavior. Soc Neurosci Abst. 10 1205, 1984. 

Figure 1. Kymographic Tracing Showing Effects of Chlordan on Blood Pressure and Respiration of Rabbit under Light Pentothal Anesthesia and Antagonistic Action of...

The antidotal action of the barbiturates is probably limited to the effects of chlordan on the nervous system. They most likely have no beneficial antagonistic action against the delayed parenchymatous degenerative changes produced by chlordan (4). Therefore, they are primarily only of possible value in acute poisoning in which severe stimulation of the central nervous system may be the primary cause of death. 

In this series, too, replacement of the N-methyl by a group such as cyclopropylmethyl leads to a compound with reduced abuse potential by virtue of mixed agonist-antagonist action. To accomplish this, reduction of 24 followed by reaction with tertiary butylmagnesium chloride gives the tertiary carbinol 27. The N-methyl group is then removed by the classic von Braun procedure. Thus, reaction with cyanogen bromide leads to the N-cyano derivative (28) hydrolysis affords the secondary amine 29. (One of the more efficient demethylation procedures, such as reaction with ethyl chloroformate would presumably be used today.) Acylation with cyclopropylcarbonyl chloride then leads to the amide 30. Reduction with lithium aluminum hydride (31) followed by demethylation of the phenolic ether affords buprenorphine (32).9... 

T. Akaike, M. Yoshida,Y. Miyamoto, K. Sato, M. Kohno, K. Sasamoto, K. Miyazaki, S. Ueda, and H. Maeda, Antagonistic action of imidazolineoxyl N-oxides against endothelium-derived relaxing factor. NO through a radical reaction. Biochemistry 32, 827-832 (1993). 

The answer is F. (Katzung, p 167, Hardman, pp 237-2382 Labetalol has potent a and p antagonist actions, due to the specific components of its racemic mixture of four isomeric compounds. Cardiac output and heart rate change minimally, while blood pressure decreases due to a overall reduction in peripheral resistance. The combined a and p antagonism has been found to be of advantage in treating pheochromocytomas. 

Lonard DM, Smith CL (2002) Molecular perspectives on selective estrogen receptor modulators (SERMs) progress in understanding their tissue-specific agonist and antagonist actions. Steroids 67 15-24... 

One of the most-studied covalent modifications is the acetylation of the lysine residues of histone tails. The acetylation state of lysines of nucleosomal histones modulates chromatin structure and regulates gene transcriptional activity. The balance of lysine acetylation is controlled by the antagonistic action of two enzyme families histone deacetylases (HDACs) and histone acetyltransferases (HATs). In humans there are essentially three main HDAC subclasses [6]. 

Dextromethorphan, contained in many nonprescription cough medicines, will produce a heavy psychedelic trip, but the nausea characteristic of the opiates may constitute a problem. Kosterlitz and Villareal (Eds.) AGONIST AND ANTAGONIST ACTIONS OF NARCOTIC ANALGESIC DRUGS (1972) and Braude et al. (Eds.) NARCOTIC ANTAGONISES (1973) are useful. 

Kretzschmar R, Meyer HJ, Teschendorf HJ, Zollner B (1969). [Antagonistic action of natural 5,6-hydrogenated kava pyrones against strychnine poisoning and experimental local tetanus]. Arch Int Pharmacodyn Ther. Dec. 182(2) 251-68. 

Boileau AJ, Newell JG, Czajkowski C. 2002. GABAa receptor P2 Tyr and Leu line the GABA-binding site insights into the mechanisms of agonist and antagonist actions. J Biol Chem 277 2931-2937. 

The plasma concentrations of caffeine in the rats exposed to the 0.25 and 1.0 mg ml solutions were within the range of those fonnd in typical users of caffeinated beverages. Caffeine may weakly stimnlate dopamine mechanisms via its antagonist action at adenosine receptors (Herrera-Marschitz et al. 1988 Casas et al. 1989 Ferre et al. 1992 Fredholm et al. 1999), and in small doses it may have enhanced the dopaminergic component in the nicotine discriminative stimulns through an effect... 

Mirtazepine (called a Noradrenaline and Selective Serotonin Antidepressant NaSSA) is the 6-aza derivative of mianserin and shares several important pharmacological properties with its predecessor, namely its antihistaminic and alpha-1 adrenoceptor antagonistic actions. Like mianserin, mirtazepine also causes weight gain. Nevertheless, mirtazepine is better tolerated and there is no evidence of blood dyscrasias associated with its clinical use. 

On a scale of 0 to 64, the individual pesticide degradations decreased from 31 to 14 when mixtures were present. This apparent antagonistic action of mixtures was probably more of a latency effect related to the six-fold increase in total pesticide concentrations rather than a toxic action to the microorganisms. 

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