Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pressure increases elicited by contractions of the circular muscle of the isolated guinea-pig vas deferens in response to nerve stimulation were recorded. In contrast to longitudinal muscle which contracted in response to 1--50 pulses, circular muscle responded only to longer trains of pulses (10--500) at a frequency of 10 Hz. Atropine (1.4 muM) caused a slight depression of responses to 100 shocks. Phentolamine at a concentration of 2.6 muM failed to inhibit the response to stimulation, but a higher concentration (53 muM) caused a definite blockade. Guanethidine (25 muM) strongly reduced the responses. With a stimulus train of 100 pulses no inhibition by prostaglandin E1 (PGE1) (0.028 muM) could be demonstrated; however, at a lower number of shocks (20--50) a clearcut depression was observed. The lower the number of pulses the more marked was the depression. The observation that PGE1 failed to block the contractions evoked by noradrenaline (59 muM) suggests a presynaptic inhibitory action of the prostaglandin. It is suggested that noradrenaline is the transmitter in both muscle coats of the guinea-pig vas deferens and that the neuroeffector junctions are sensitive to the effect of PGE1.
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PMID:Inhibition of neuromuscular transmission by prostaglandin E1 in the circular muscle of the guinea-pig vas deferens. 18 81

Because of the multiplicity of disease conditions and diminished tolerance for drugs in the aged, it is necessary to know concomitant pathologic conditions to determine which antihypertensive drug to use. In the Philadelphia Geriatric Center, there are about 1,000 residents, between 70 and 100 years of age. About 40% have hypertension; almost 50% have or once had depression; there are many cases of hiatal hernia and/or peptic ulcer; in one subdivision of residents, almost 40% have renal disease with BUN above 30 mg/100 ml. In antihypertensive treatment, some individuals respond fairly well to reassurance and weight reduction, when obese, even without drugs. All are given a low-salt diet. A diuretic is first used--thiazide in cases of good renal function, furosemide with impaired renal function. Liquid potassium supplements are given. If there is but little reduction in blood pressure in several weeks, methyldopa is added in ascending doses, in cases with or without renal impairment. In hypertension with impaired renal function, furosemide and/or methyldopa were especially valuable. Furosemide as an antihypertensive drug was also noted to delay the onset of congestive heart failure. Since reserpine can aggravate peptic ulcer and can precipitate or aggravate depression, it should seldom be used to treat hypertension in the aged. Guanethidine is rarely used, since it can cause cerebrovascular insufficiency and marked weakness. High blood pressure should be reduced slowly in the aged, to avoid untoward effects.
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PMID:An approach to the treatment of hypertension in the aged. 105 27

The present experiments were undertaken to determine, using Laser Doppler flowmetry, if elimination of efferent constrictor mechanisms would unmask cutaneous vasodilator responses following preganglionic sympathetic nerve stimulation in the forepaw of anesthetized cats. We also addressed the question of a potential causal relationship between neurally evoked vasodilator and sudomotor responses. Three separate anti-adrenergic regimens were utilized: (1) acute guanethidine administration (1-2 mg/kg); (2) chronic monoamine depletion with reserpine (5 mg/kg) and alpha-methyl-para-tyrosine (2 x 300 mg/kg); and (3) alpha-adrenoceptor blockade with prazosin (300 micrograms/kg) and yohimbine (0.5 mg/kg). Guanethidine treatment produced a significant depression of basal cutaneous blood flow whereas alpha-adrenoceptor blockade did not. In all three groups, stimulation of the preganglionic thoracic sympathetic nerve trunk produced intensity-dependent increases of digital skin blood flow along with near-maximal sympathetic-cholinergic sudomotor (electrodermal) responses recorded simultaneously from the same paw. Vasodilator responses were not altered by intravenous propranolol (1 mg/kg) or atropine (1 mg/kg); however, evoked sudomotor responses were totally blocked by atropine. Low doses (1.5 mg/kg i.v.) of hexamethonium selectively abolished the cutaneous vasodilator responses but not concomitantly evoked sudomotor responses. These results demonstrate, using direct measurements of blood flow, that cutaneous digital vasodilation can be measured in cats following removal of vasoconstrictor mechanisms either pre- or postjunctionally. Neither muscarinic nor beta-adrenoceptor mechanisms appear to be involved. These experiments also suggest that cutaneous vasodilation is not a consequence of concomitant sudomotor activation.
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PMID:Neurogenic cutaneous vasodilation in the cat forepaw. 135 May 98

The association between antihypertensive medications and depression has been recognised for over 40 years. More recently, our understanding of the role of neurotransmitters in the aetiology of depression has helped us understand how antihypertensive drugs cause depression. Biogenic amine depletion is now believed to underlie the organic nature of depression, and many of the drugs used to treat hypertension interfere with this system. There is now compelling evidence that both reserpine and alpha-methyldopa can induce or worsen depression through their actions on the central nervous system. beta-Blockers have also been implicated, but the data supporting the link between these drugs and depression are not as certain. Guanethidine, clonidine, hydralazine, and prazosin appear to pose little risk in causing depression, although rare occurrences have been reported. Diuretics, calcium channel blockers, and angiotensin converting enzyme (ACE) inhibitors appear to have the lowest association with depression and are therefore the drugs of choice when depression is a risk. Physicians should know which drugs introduce the risk of causing or worsening depression. The wide array of medications now available to treat hypertension offers alternatives that pose low risk. All patients receiving medication to treat hypertension should be evaluated periodically for depression, and if depression occurs, medication should be suspected as playing a role in its aetiology.
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PMID:Antihypertensive medications and depression. 207 96

1 Secretory potentials produced by stimulation of the salivary duct nerves were recorded intracellularly from cockroach isolated salivary glands. The secretory potential normally consisted of a 40-80 mV hyperpolarization of the gland cell.2 Bretylium (0.1-1 mM) reduced the amplitude of the secretory potential without affecting the response of the gland to dopamine (0.25-1 muM). In addition, bretylium caused an increase in the frequency of miniature secretory potentials and the appearance of nerve terminal action potentials.3 Guanethidine (1 mM) reduced the response to nerve stimulation without depressing the sensitivity of the salivary gland to dopamine (0.25-0.5 muM) and without causing an increase in the occurrence of miniature potentials. Higher concentrations (4-5 mM) completely eliminated secretory potentials but also reduced the sensitivity of the gland cell to dopamine.5 These results indicate a presynaptic depression of the secretory potential by both bretylium and guanethidine. It is suggested that, in this system, bretylium acts by depolarizing the nerve terminal while guanethidine does not.
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PMID:The effects of bretylium and guanethidine on catecholaminergic transmission in an invertebrate. 437 27

1. Infusion of daunomycin 50 mg/kg in the monkey consistently induced ventricular arrhythmias which were not influenced by bilateral vagotomy.2. A central sympathetic component to the arrhythmias was suggested because spinal transection, ganglionic blockade or bilateral stellate ganglionectomy prevented any alterations in the e.c.g.3. Bilateral adrenalectomy or splanchnic nerve section protected three of six animals. This source of catecholamines may not be necessary in every case to initiate the arrhythmia.4. Guanethidine was a relatively ineffective antiarrhythmic agent. Timing appears to be important with this agent.5. Pargyline, by monoamine oxidase inhibition or other mechanisms, significantly lowered the arrhythmic dose of daunomycin. Reserpine pretreatment, on the other hand, prevented any e.c.g. alterations following daunomycin.6. Phenoxybenzamine exerted significant protection which may be related to its cardiodepressant properties.7. Alterations in e.c.g. were seen in all (+)-propranolol pretreated animals, although the arrhythmic period was modified in two of three experiments. Racemic (+/-) propranolol, which exerts direct myocardium depression as well as beta-adrenoceptor blockade, was completely protective in four of five experiments. The results of the present experiments indicate that the sympathetic nervous system is intimately involved in the daunomycin arrhythmia.
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PMID:Role of the sympathetic nervous system in daunomycin-induced arrhythmia in the monkey. 499 May 92

Intracellular recordings were made in a mid-pontine slice preparation of the rat brain containing the nucleus locus coeruleus. Focal electrical stimulation evoked biphasic synaptic potentials consisting of early depolarizing (d.p.s.p.) and late hyperpolarizing (i.p.s.p.) components. The alpha(2)-adrenoceptor antagonist idazoxan inhibited the i.p.s.p. without altering the d.p.s.p. All of the following experiments were carried out in the presence of kynurenic acid and picrotoxin to block the glutamatergic and GABAergic fractions of the d.p.s.p., respectively. Guanethidine, which is known to inhibit noradrenaline and ATP release from nerve terminals of postganglionic sympathetic nerves, depressed both the d.p.s.p. and the i.p.s.p. in a concentration-dependent manner. Damage of catecholaminergic nerve terminals by 6-hydroxydopamine also decreased both the d.p.s.p. and the i.p.s.p. The P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) depressed the d.p.s.p., whereas the i.p.s.p. remained unaffected. The further application of PPADS did not increase the depression of the d.p.s.p. by guanethidine. Superfusion with the mixed alpha-adrenoceptor agonist noradrenaline or the selective P2 receptor agonist adenosine 5'-O-(2-thiodiphosphate) inhibited both the d.p.s.p. and the i.p.s.p. The inhibitory effects of these agonists were prevented by the respective antagonists idazoxan or suramin. In the presence of suramin noradrenaline failed to inhibit the residual d.p.s.p. Superfused noradrenaline potentiated rather than inhibited responses to pressure-applied alpha,beta-methylene-ATP; superfused adenosine 5'-O-(2-thiodiphosphate) did not interact with pressure-applied noradrenaline. In conclusion, we present electrophysiological evidence for the co-release of ATP and catecholamines in the CNS. At the cell somata of neurons in the locus coeruleus, noradrenaline and ATP activate inhibitory alpha(2)-adrenoceptors and excitatory P2 receptors, respectively. In addition, inhibitory presynaptic autoreceptors of the alpha(2) and P2 types appear to regulate release of the two co-transmitters.
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PMID:Co-transmitter function of ATP in central catecholaminergic neurons of the rat. 1122 96

Effective therapy (Rx) in primary hypertension (PH) for 50 years, has featured sympathetic nervous system (SNS) mechanisms. Ganglionic blockers and reserpine were pre-eminent in the 1940s (mydriasis, ileus, impotence, peptic ulcer). Guanethidine, and in the 1960s clonidine and methyldopa, were step II agents to thiazide Rx in the 1950s. Reserpine depletes brain (depression) and peripheral (PPH) noradrenaline (NA) storage sites, guanethidine depleted NA storage via blockade of reuptake. Venomotor sympathoplegia resulted in postural hypertension. An analogue, metaiodobenzyguandine is used in diagnosis and Rx of pheochromocytoma. Clonidine lowers both central and PPH neuronal NA release via both stimulation of alpha agonist adrenoreceptors (sedation) and specific imadazoline binding sites (IBS). Methyldopa lowers pressure via PPH induced NA release (retrograde ejaculation) and via alphamethyl NA on central alpha-2 receptors (depression). The alpha-2 and alpha-2 receptor antagonists (alphaRA) cause reflex tachycardia and first-dose hypotension. Recently a two-fold incidence of congestive heart failure after alphaRA in treated primary hypertensives question their role in PH. The beta RA, with or absent alphaRA, remain premier since the 1970s due to mortality benefit in systolic dysfunction and post myocardial infarction, certifying the role of the SNS in the pathogenesis and sequelae and Rx of PH. The future includes beta RA, specific IBS agents, angiotensin (AII) RA with avid presynaptic AII affinity and vasopeptidase inhibitiors that raise peptides and suppress SNS.
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PMID:Sympatholytic therapy in primary hypertension: a user friendly role for the future. 1198 8

The chief dangers reported with some common drugs are reviewed. Hazards of antibiotic therapy include: the increasing incidence of sensitization to penicillin with occasional anaphylactic reactions; aplastic anemia with chloramphenicol, and the poor tolerance of infants for chloramphenicol; staphylococcal enterocolitis; unnecessary "prophylactic" use of antibiotics. Thiazide diuretics may precipitate potassium depletion, skin reactions, pancreatitis, blood dyscrasias, gout, diabetes mellitus and hepatic coma. Reserpine can increase gastric acidity, induce mental depression, and when used with digitalis lead to ventricular premature beats. Hydralazine may aggravate angina pectoris, cause tachycardia, and bring about a syndrome resembling disseminated lupus erythematosus. Guanethidine may result in loose stools, impotence, and postural hypotension. Hazards of phenothiazines include jaundice, parkinsonian states and tremors, convulsions, hypotension, and blood dyscrasias. The butanediols have numerous side effects including gastrointestinal, cutaneous and hypotensive reactions. Prolonged corticosteroid therapy introduces a new danger in surgical treatment. The progesterone-like drugs may induce masculinization of the female fetus.
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PMID:Dangers in the use of some potent drugs. 1398 37