Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although prevention of heart failure recently has become a realistic issue, management of heart failure once the syndrome has developed, is mainly supportive, based on the various cardiac and peripheral changes which occur in the course of heart failure. Of these, abnormal neurohormonal activation is of major pathophysiologic and prognostic significance. Consequently, modulation of neuroendocrine activation is now recognized a prime target in the treatment of heart failure, besides diuretic therapy. In this respect, the value of converting enzyme inhibition is well established. Future developments in this area include dopaminergic agents, vasopressin antagonists, angiotensin II receptor antagonists, renin inhibitors, spironolactone and, possibly, ANF peptidase inhibitors. Besides diuretics, necessary when signs of fluid retention are present, the approach to heart failure management involves other pharmacologic issues. In view of abnormal vascular control with vasoconstriction prevailing during progressive heart failure, it clearly makes sense to vasodilate. However, of available vasodilators, only the combination of relatively high dose nitrates and hydralazine has proven to be of clinical significance, in terms of hemodynamics, exercise capacity and survival. It is possible, though, that novel generation dihydropyridine derivatives may prove beneficial as well. Thus far, there has been much debate concerning the usefulness and particularly the safety of positive inotrope therapy and inodilator treatment. Taken together, this concern relates to presence and predominance of cAMP-dependent mechanisms to induce these effects. Thus, sympathomimetic agents and phosphodiesterase inhibitors, such as milrinone or enoximone, are without beneficial effects, but instead shorten survival during long-term therapy. This may be different where compounds which act through cAMP-independent mechanisms, i.e., calcium sensitization or sodium channel stimulation, are concerned, but needs to be confirmed yet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Congestive heart failure. Drug therapy: central or peripheral approach? 791 52

Autonomic dysfunction is responsible for much of the morbidity associated with frequently encountered neurological disorders, such as Parkinson's disease, multiple sclerosis, cerebrovascular disease, and peripheral neuropathies, as well as with the rarer primary autonomic nervous system degenerations. We review the treatment of those aspects of autonomic dysfunction that often present to the neurologist, including orthostatic hypotension, urinary incontinence and retention, and bowel dysmotility syndromes. Pathophysiology is discussed in each instance as it relates to a rational approach to therapy. For management of orthostatic hypotension, we review the use of mineralocorticoids, direct and indirect sympathomimetic agents, other pressors, dopamine-blocking agents, vasopressin receptor agonists, and others. Treatment of urinary incontinence and retention is addressed, with attention to drugs that modulate bladder contractility and bladder outlet resistance. Therapies for bowel dysmotility syndromes (such as gastroparesis, diarrhea, and fecal incontinence) are described, including bulk agents, laxatives, prokinetic agents, and antidiarrheal drugs.
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PMID:The treatment of autonomic dysfunction. 845 96

ANAESTHETICS, ENDOCRINE SYSTEM, AND STRESS: The effects of anaesthetics on the nervous system are invariably associated with endocrine reactions, which are of great importance for the general characterization of anaesthetics or anaesthetic regimens. In this context, the endocrine stress response is mainly represented by adrenaline (A), noradrenaline (NA), antidiuretic hormone/vasopressin (ADH), adrenocorticotropic hormone (ACTH), and cortisol. PHARMACOLOGICAL PROFILE AND ANAESTHETIC ACTION OF KETAMINE: The pharmacological profile of ketamine is characterized by the term "dissociative anaesthesia." At the present time, the anaesthetic action of ketamine cannot be explained by a single mechanism. Its overall action might be due to different central and peripheral factors, and stereospecific effects are obvious. ENDOCRINE RESPONSES TO RACEMIC KETAMINE AND S(+)-KETAMINE: In contrast to stereospecific differences in the anaesthetic action of racemic ketamine and S-(+)-ketamine, the endocrine reactions to the S-(+) isomer and the racemic mixture are very similar. When S(+)-ketamine is used as the sole anaesthetic, significant activation of the sympathoadrenergic system with increases in plasma levels of A and NA can be observed. This effect is mitigated by midazolam. In combination with propofol, sympathoadrenergic responsiveness is preserved without overwhelming effects. In contrast to monoanaesthesia with S(+)-ketamine, during combination with midazolam and propofol significant increases in plasma ADH levels are observed, which might be due to suppressed sympathoadrenergic reactivity. In addition, surgical stress activates the pituitary-adrenocortical system with increases in ACTH and cortisol. Effects of midazolam and propofol on this effect are similar. SYNOPSIS AND CLINICAL ASPECTS: S-(+)-ketamine as a monoanaesthetic has significant sympathomimetic properties, which are beneficial during induction of patients in shock and patients with asthma. The combination of S-(+)-ketamine and midazolam has weaker sympathomimetic and general endocrine-stimulating properties, and can be used for analgosedation in patients with cardiovascular instability and exogenous catecholamine requirements. In combination with propofol, the sympathomimetic and general endocrine-stimulating effects of S-(+)-ketamine are less pronounced because of contrasting properties of both drugs. This combination might be useful in patients with endocrine deficits and for analgosedation, when rapid recovery is necessary and negative circulatory effects should be avoided.
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PMID:[Endocrine reactions following S-(+)-ketamine]. 916 76

Quantitative structure-activity relationships (QSARs) of different cardiotonic agents are presented. A critical analysis of all QSARs provides a very vivid picture of the mechanisms of varying cardiotonic agents. The cardiotonics can be broadly put into 2 categories: cardiac glycosides and nonglycoside cardiotonics, which include phosphodiesterase of type III (PDE III) inhibitors, sympathomimetic (adrenergic) stimulants, A1-selective adenosine antagonists, Ca2+ channel activators and vasopressin antagonists. For cardiac glycosides, QSARs reveal that the position of carbonyl oxygen in their lactone moiety and shifting of the lactone ring from its original position or its replacement by another group would be crucial for their activity. The carbonyl group or its isostere like CN is indicated to be the sole binding entity and the hydrogen bonding through this group is considered to be the most likely binding force. For nonglycoside cardiotonics that include PDE III inhibitors and A1-selective antagonists, a five-point model has been established for their activity, the salient features of which are: (1) the presence of a strong dipole, (2) an adjacent acidic proton, (3) a methyl-sized lipophilic space, (4) a relatively flat overall topography and (5) a basic or hydrogen-bond acceptor site opposite to the dipole. For Ca2+ channel activators, the importance of steric, electrostatic, lipophilic and hydrogen-bonding properties of molecules is indicated, while for vasopressin antagonists the lipophilic and electronic properties are suggested to be the most important.
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PMID:Quantitative structure-activity relationships of cardiotonic agents. 1112 65

We have shown previously that histaprodifen and its Nalpha-substituted analogues methylhistaprodifen and dimethylhistaprodifen are highly potent H1-receptor agonists in vivo. The aim of the present study was to examine the influence of four newly synthesized histaprodifen analogues, 3-fluoro-methylhistaprodifen (1), Nalpha-imidazolylethylhistaprodifen (2), bis-histaprodifen (3) and Nalpha-methyl-bis-histaprodifen (4), on the cardiovascular system in the pithed and in the anaesthetized rat. In pithed and vagotomized rats, diastolic blood pressure (which was increased to 80-85 mmHg by vasopressin infusion) was decreased dose dependently by methylhistaprodifen (the reference compound) and by compounds 1-4. The maximum decrease was about 47-50 mmHg for methylhistaprodifen and compounds 1, 2 and 3. Their potencies, expressed as pED50 (the negative logarithm of the dose in mole per kilogram body weight that decreased diastolic blood pressure by 25 mmHg), were 8.31, 8.23, 8.26 and 7.84, respectively. With compound 4 the maximal effect was not achieved at doses up to 1 micromol/kg (the latter dose decreased blood pressure by about 30 mmHg; pED50 approximately 6.5). The vasodepressor effect of the five compounds was attenuated by the H1-receptor antagonist dimetindene (1 micromol/kg) but was not changed by combined administration of the H2- and H3-receptor antagonists ranitidine and thioperamide (1 micromol/kg each), by combined administration of the alpha1- and alpha2-adrenoceptor antagonists prazosin and rauwolscine (1 micromol/kg each) or by the beta-adrenoceptor antagonist propranolol (3 micromol/kg). In anaesthetized rats methylhistaprodifen and compounds 1-4 induced almost the same fall in blood pressure as in pithed and vagotomized animals; the effects were sensitive to blockade by dimetindene (1 micromol/kg). Higher doses of compounds 1 and 2 (1 micromol/kg) increased heart rate in pithed and vagotomized rats in a manner sensitive to propranolol (3 micromol/kg) but insensitive to dimetindene (3 micromol/kg). The same dose of methylhistaprodifen and of compounds 3 and 4 failed to affect heart rate. We conclude that the agonistic potency of compounds 1 and 2 at H1-receptors in the cardiovascular system of the rat equals that of methylhistaprodifen, the most potent histamine H1-receptor agonist available until recently. Compounds 1 and 2 exhibit sympathomimetic activity at high doses.
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PMID:Novel histaprodifen analogues as potent histamine H1-receptor agonists in the pithed and in the anaesthetized rat. 1148 33

When the nervous component of the vasomotor tone of the blood vessels of the innervated rat hind limb perfused with blood was reduced by ganglion blockade, by section of the nerves to the hind limb, or by the indirect effect of drugs, the vasoconstrictor response of the blood vessels to noradrenaline was immediately increased. This increased peripheral response was observed only when the blood perfusing the hind limb was from the same animal or from a genetically similar animal. Reduction of the nervous component of the vasomotor tone also increased the constrictor response of the hind-limb blood vessels to adrenaline, ephedrine, tyramine and 5-hydroxytryptamine, but did not increase the response to angiotensin, vasopressin or S-methyl isothiourea. Pre-treatment with reserpine increased the hind-limb response to noradrenaline but reduced the response to ephedrine, tyramine and 5-hydroxytryptamine. The results suggest that, in rats, activity in the sympathetic nervous system directly influences the reactivity of peripheral blood vessels to noradrenaline and other sympathomimetic drugs.
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PMID:Relation in rat hind-limb blood vessels between nervous vasomotor tone and the response to vasoconstrictor drugs. 1446 29

Pediatric incontinence is a bothersome symptom for children and their parents. It can have a profound influence on a child's social and psychologic development and well-being. It is important to understand the different disorders that result in incontinence and also to understand the neural influences and development on urinary control. Urinary leakage can be a functional or organic disorder, with many possible etiologies. The most common group of pediatric patients with incontinence are those with overactive bladder disorder. Pharmacologic therapy centers on the blockage of muscarinic receptors by the tertiary amines such as oxybutynin, tolterodine, trospium chloride, and propiverine. Although most novel anticholinergic medications are effective and well tolerated in children, in our experience oxybutynin extended release provides superior relief for urge urinary incontinence in children. Other agents such as alpha-adrenoceptor antagonists have been used with success to improve bladder empyting and decrease outlet resistance. Night-time voiding disorders such as primary monosymptomatic nocturnal enuresis tend to be symptomatically treated. One of the mainstays of pharmacotherapy is desmopressin, an analog to antidiuretic hormone, which decreases night-time urine production. Tricyclic antidepressants such as imipramine have also been used successfully through a combined mechanism of action believed to be the result of anticholinergic, antispasmodic, and sympathomimetic effects. Often the successful treatment of constipation also treats urinary incontinence or at least the symptoms of urinary leakage are improved. The new non-absorbable, tasteless, and odorless PEG-3350 (polyethylene glycol 3350) powder has quickly become a mainstay of the pharmacologic treatment for constipation because of its ease of preparation and favorable adverse effect profile. A better understanding of the physiologic control, cellular interactions, and second messenger signal transduction pathways has led to the development of many new potential target sites for pharmacologic intervention. The advancement of new uroselective muscarinic antagonists is currently under investigation for agents such as darifenacin and temiverine, which have the potential to improve efficacy without increasing unwanted adverse effects. New pharmacologic delivery systems are also being developed ranging from intravesical to transdermal applications to change biodistribution and improve selectivity. Incontinence is a significant problem for children, their parents, and their physicians. The changing and advancing field of pharmacotherapy has made big strides for symptom control in this patient population.
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PMID:Contemporary and emerging drug treatments for urinary incontinence in children. 1597 61

The bed nucleus of the stria terminalis (BST) is a limbic structure involved in regulating the hypothalamic-pituitary-adrenal axis as well as in central cardiovascular control. We report here on cardiovascular effects caused by microinjection of noradrenaline (NA) in the BST of the rat brain and the peripheral mechanisms involved in their mediation. Injection of NA (3, 7, 10, 15, 30, or 45 nmol in 100 nl) in the BST of unanesthetized rats caused long-lasting dose-related pressor and bradycardiac responses. No responses were observed when the dose of 10 nmol NA was microinjected into surrounding structures, such as the anterior commissure, the stria terminalis, the fornix, and the internal capsule, indicating a predominant action at the BST. Additionally, microinjection of 50 nmol tyramine, an indirectly acting sympathomimetic amine, caused similar pressor response, indicating local NA release in the BST. Responses to NA microinjection in the BST were markedly reduced in urethane-anesthetized rats, favoring the idea of a central action without significant leakage to the peripheral circulation. The pressor response was potentiated by i.v. pretreatment with the ganglion blocker pentolinium and blocked by i.v. pretreatment with the selective V(1)-vasopressin antagonist dTyr(CH(2))(5)(Me)AVP, suggesting its mediation by vasopressin release into circulation. The bradycardiac response to NA microinjected into the BST was also abolished by pretreatment with the vasopressin antagonist, indicating its reflex origin. In conclusion, results indicate that microinjection of NA into the BST evokes pressor responses, which are mediated by acute vasopressin release.
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PMID:Cardiovascular effects of noradrenaline microinjection in the bed nucleus of the stria terminalis of the rat brain. 1733 Feb 75

Cocaine is an indirect sympathomimetic agent that acts in the nervous system to block the presynaptic reuptake of serotonin and catecholamines (dopamine, norepinephrine and epinephrine) and to increase their bioavailability at the post-synaptic receptors. The association of cocaine and hyponatremia has not been reported in adults. We describe a case of acute severe hyponatremia that followed smoking cocaine. We propose that cocaine, via its effect on the neurotransmitters, stimulates antidiuretic hormone release and leads to a syndrome of inappropriate antidiuretic hormone secretion.
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PMID:Cocaine-associated acute severe hyponatremia. 2126 86


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