Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chronotropic effects of midodrine, glycine (10(-8) to 3.10(-3) M), ST1059 and methoxamine (10(-8) to 10(-3) M) were investigated in the spontaneously beating guinea-pig right atrial preparation. Midodrine and glycine produced a slight, but significant rise in atrial rate over a wide concentration range. The midodrine-induced rise in atrial rate was not influenced by the beta-adrenergic receptor blocking drug propranolol (10(-6) M). The histamine (H2)-receptor blocking drug metiamide (3.10(-5) M) abolished the positive chronotropic actions of both midodrine and glycine. No positive chronotropic effect was seen after the administration of ST 1059 or methoxamine. A decrease in atrial rate was elicited by high concentrations (above 10(-4) to 10(-3) M) of the sympathomimetic agents midodrine, ST 1059, and methoxamine, but not by the amino acid glycine.
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PMID:Effects of midodrine, ST 1059, methoxamine and glycine on spontaneously beating guinea-pig atria. 6 15

Pharmacodynamic actions of alpha-(2,5-dimethoxyphenyl)-beta-glycinamido-ethanol-hydrochloride (midodrine, Gutron) and alpha-(2,5-dimethoxy-phenyl)-beta-aminoethanol (ST 1059), the main metabolite of midodrine, were investigated in various experimental procedures. Midodrine raises arterial blood pressure both after parenteral and enteral administration in animal experiments. Midodrine increases peripheral vascular tone when given in doses still ineffective in raising blood pressure. The d(+)-isomer of midodrine is by far less effective than the racemic mixture. Pretreatment with atropine, reserpine, guanethidine or hexamethonium has no influence on midodrine activity. Midodrine effects are greatly reduced by phentolamine but rather enhanced by propranolol pretreatment. Midodrine raises blood pressure in pithed rats, too; in the experiments performed the drug is devoid of central effects even when high doses are given. Chronic pretreatment with midodrine over a longer period reduces the effect of a subsequent single injection of this substance. Because of the results cited above midodrine may be classified as a direct peripheral alpha-adrenergic stimulating agent. alpha-Adrenergic receptor stimulation induced by midodrine can be demonstrated in various smooth muscle organs (blood vessels, nictitating membrane, intestine, pupil, urinary bladder, bronchi). In contrast to other pressor sympathomimetic agents, midodrine is of long duration of action and good efficacy after enteral administration. ST 1059, the main metabolite of midodrine, is an active alpha-adrenergic stimulating agent with a shorter duration of action than midodrine. It is suggested that midodrine is the well-absorbed "transport form", from which ST 1059, the actural pressor agent, is formed enzymatically in organism.
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PMID:Pharmacodynamic actions of midodrine, a new alpha-adrenergic stimulating agent, and its main metabolite, ST 1059. 6 56

For 10 days 21 female patients with clinical stages I to III stress incontinence and 4 continent control female patients were treated with the alpha-sympathomimetic midodrine. Urethrometry revealed that alpha-adrenergic stimulation resulted in an increase in the urethral occlusion pressure of up to 30 per cent and, cystometrically, to an increase in the detrusor pressure of up to 35 per cent without impairment of bladder capacity. In the stage I group 83 per cent and in the stage II group 63 per cent of the patients became continent. Midodrine, the advantage of which over comparable sympathomimetics, such as ephedrine, synephrine and norphenylephrine, lies in the absolutely sure and sustained action in oral use, is recommended as an alternative therapy to traditional surgical procedures in the treatment of stages I and II female stress incontinence.
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PMID:Treatment of female stress incontinence with midodrine: preliminary report. 7 32

The long-term treatment of retrograde ejaculation disorders following retroperitoneal lymphadenectomy with the alpha-sympathomimetic, Midodrin, administered orally, led to improvements in the intensity of orgasm and the degree of erection. Normal ejaculation was induced in 7 out of 12 patients and emission of spermatozoa into the posterior urethra was restored in 3 out of 12 patients by a single intravenous injection of 25--30 mg Midodrin.
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PMID:The use of Midodrin in the treatment of ejaculation disorders following retroperitoneal lymphadenectomy. 8 24

To clarify the effect of a long-acting selective alpha 1-adrenoceptive sympathomimetic agent on sympathetic outflow to muscles (muscle sympathetic activity, MSA) in humans, 5 mg of midodrine hydrochloride was injected intravenously in ten healthy male subjects aged 19-25. Spontaneous MSA was significantly suppressed as well as plasma norepinephrine level without changing heart rate, or systemic blood pressure. The suppression continued for more than 90 min, and this is supposed to be due to negative feedback action on the baroreflex loop. The absence of significant changes in heart rate or systemic blood pressure in healthy subjects suggests that hemodynamic homeostasis is maintained by reducing the MSA in response to a long-acting sympathomimetic agent, like midodrine hydrochloride, which constricts peripheral vessels directly.
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PMID:Long-acting alpha 1-adrenoceptive sympathomimetic agent suppresses sympathetic outflow to muscles in humans. 172 5

Midodrine, a peripheral alpha-adrenergic agonist, finds use in the clinical management of patients with orthostatic hypotension or hypotension secondary to other clinical conditions or drug therapies. Midodrine is almost completely absorbed after oral administration and undergoes enzymatic hydrolysis to form its pharmacologically active metabolite, de-glymidodrine. In patients with refractory orthostatic hypotension oral midodrine increases standing blood pressure and improves symptoms of orthostatism, such as weakness, syncope, blurred vision and fatigue, without any associated cardiac stimulation. Comparative studies have shown midodrine to be clinically at least as effective as other sympathomimetic agents (norfenefrine, etilefrine, dimetofrine and ephedrine) and dihydroergotamine in this regard. Additionally, midodrine appears to cause less frequent and severe adverse effects associated with alpha-receptor agonism such as piloerection and urinary hesitancy. The most commonly experienced adverse effects--piloerector reactions, gastrointestinal disorders, and cardiovascular complaints--are generally mild and can be controlled by reducing the dosage of midodrine. Thus, midodrine is at least as useful as other currently available options in the management of orthostatic or secondary hypotension, and represents a stepping stone towards optimal therapy.
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PMID:Midodrine. A review of its pharmacological properties and therapeutic use in orthostatic hypotension and secondary hypotensive disorders. 248 Aug 81

In two groups of volunteers pharmacological parameters of the antihypotensive drug midodrine have been investigated. The first group of 12 male healthy volunteers received 2.5 mg midodrine hydrochloride intravenously, as drinking solution or as tablet according to a randomized cross-over design. Plasma and urine samples were analyzed for midodrine and its main metabolite ST 1059 by high-performance liquid chromatography. The mean maximum concentration in plasma for midodrine was 10 ng/ml 20-30 min after oral administration, for ST 1059 5 ng/ml after 1 h. Midodrine was eliminated with a terminal half-life of 0.5 h, ST 1059 with a half-life of 3 hrs. The mean area under the plasma-level vs. time curve (AUC) of ST 1059 after administration of 2.5 mg midodrine i.v. was 28.7 ng x h/ml, and similar for the other formulations which are considered to be bioequivalent. In a second group of 15 volunteers with postural hypotension midodrine (M) as alpha-sympathomimetic drug and oxilofrine (O) as beta-sympathomimetic drug was given i.v. in a randomized double blind study against placebo (P). Blood pressure (BP), heart rate (HR) and circulating catecholamines (CA) were determined before and after injections of the drugs as well as before and during 10 min of tilting. Echocardiographic parameters were obtained at rest before and after the administration of the drugs. Blood pressure remained unchanged at rest and during orthostasis after all agents injected. After oral administration of midodrine heart rate was decreased and systolic blood pressure increased significantly and dose-dependently. M lowered circulating noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetic parameters and haemodynamic actions of midodrine in young volunteers. 769 Mar 82

Chronic low blood pressure is typically accompanied by symptoms such as fatigue, reduced drive, dizziness, headaches and cold limbs. Reduced cognitive performance, diminished cerebral blood flow and autonomic dysregulation have been furthermore documented in this condition. The present contribution reports two studies exploring systemic hemodynamics in chronic hypotension and their modification through vasopressor application. In study I, effects of the alpha-sympathomimetic midodrine were examined in 54 hypotensive individuals using a placebo-controlled double-blind design. Hemodynamic parameters were assessed at rest and during mental stress. They were derived from continuous blood pressure recordings using Modelflow analysis. The drug led to marked increases in blood pressure, total peripheral resistance and stroke volume. However, due to strong heart rate deceleration, cardiac output remained virtually unchanged. In study II, 40 hypotensive and 40 normotensive control persons were compared with respect to hemodynamics. While groups did not differ in total peripheral resistance, hypotensives exhibited markedly diminished stroke volume and heart rate, resulting in a reduction in cardiac output of 25% at rest and of 33% during mental stress. The data provide relevant knowledge about the hemodynamic mediation of chronic hypotension. In contrast to elevated blood pressure, which is mainly determined by increased peripheral resistance, reduced cardiac output may be the cardinal hemodynamic aberration in chronic hypotension. Midodrine proved to be effective in elevating blood pressure. However, given the cardiac origin of chronic hypotension and the lack of drug effect on cardiac output, alpha-sympathomimetic treatment may be suboptimal.
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PMID:Hemodynamic determinants of chronic hypotension and their modification through vasopressor application. 1934 May 50

Midodrine is an oral, peripherally acting alpha-adrenergic agonist. After gaining Food and Drug Administration (FDA) approval in 1996 for orthostatic hypotension, its use has evolved to target vasoplegic conditions such as intradialytic hypotension in the end-stage renal disease population, refractory ascites in cirrhotic patients to support diuresis, and in hepatorenal syndrome. Upon oral ingestion, the drug undergoes enzymatic hydrolysis to an active metabolite, desglymidodrine. Its use has been well tolerated at 2.5 mg, 5 mg, and 10 mg oral doses. The most frequently occurring side effects relate directly to its sympathomimetic profile and include piloerection, scalp pruritis, generalized paresthesias, and urinary retention. The vasoplegic profile of sepsis would be a potential target for midodrine therapy. While its use to mediate recovery from septic shock has been suggested, there is a paucity of clinical data supporting its use. Such therapy may be uniquely appropriate in septic patients who are not candidates for intensive care unit (ICU) level of care.
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PMID:The Role of Midodrine for Hypotension Outside of the Intensive Care Unit. 2887 93