Norepinephrine antagonists

Category Norepinephrine antagonist Serotonin antagonist Half-life I. I hours... 

Agonists isoproterenol > epinephrine > norepinephrine Antagonists oetaxolol > ICI 118,551 Pi-adrenergic receptors... 

Prazosin, a selective a -adrenoceptor antagonist, exerts its antihypertensive effect by blocking the vasoconstrictor action of adrenergic neurotransmitter, norepinephrine, at a -adrenoceptors in the vasculature (200,227,228). Prazosin lowers blood pressure without producing a marked reflex tachycardia. It causes arteriolar and venular vasodilation, but a significant side effect is fluid retention. Prazosin increases HDL cholesterol, decreases LDL cholesterol, and does not cause glucose intolerance. 

Ethanol also reduces the activity of the noradrenergic system in the locus coeruleus, and alterations in norepinephrine activity may account for some aspects of intoxication and the abstinence syndrome. The 0.2 antagonist clon-idine and the P-receptor antagonist propranolol reduce some symptoms of alcohol withdrawal (Bailly et al. 1992 Carlsson and Fasth 1976 Dobrydnjov et al. 2004 Kahkonen 2003 Petty et al. 1997 Wong et al. 2003). 

MAOI, monoamine oxidase inhibitor SARI, serotonin antagonist and reuptake inhibitor SNRI, serotonin and norepinephrine reuptake inhibitor SSRI, selective serotonin reuptake inhibitor TCA, tricyclic antidepressant. 

Figure 3 Putative model for the mechanism by which biogenic amines stimulate CE secretion across the rabbit corneal epithelium. Epn = epinephrine Nep = norepinephrine Tim = Timolol Ser = serotonin Msg = methysergide Dop = dopamine Hal = haloperi-dol (E = (E-adrenoceptor AC = adenylate cyclase. The scheme is consistent with the observation that epithelial responsiveness to serotonin and dopamine can be blocked by their receptor antagonists haloperidol and methysergide, respectively, and by both timolol treatment and sympathectomy. The probable source of serotonin or dopamine is the sympathetic fibers that innervate the cornea. (From Ref. 284.)...

The major circulating hormones that influence vascular smooth muscle tone are the catecholamines epinephrine and norepinephrine. These hormones are released from the adrenal medulla in response to sympathetic nervous stimulation. In humans, 80% of catecholamine secretion is epinephrine and 20% is norepinephrine. Stimulation of cy-adrenergic receptors causes vasoconstriction. The selective a,-adrenergic receptor antagonist, prazosin, is effective in management of hypertension because it causes arterial and venous smooth muscle to relax. 

Angiotensin II causes vasoconstriction by direct stimulation of ATj receptors on the vascular smooth muscle. It also enhances release of the neurotransmitter norepinephrine from the sympathetic nerve fibers present in the blood vessels. The vasopressor effects of Ag II may be inhibited pharmacologically in order to decrease TPR and treat hypertension. An important class of orally active drugs is the ACE inhibitors, including captopril and enalopril, which prevent formation of Ag II. More recently, angiotensin receptor antagonists have been developed that act at the vascular smooth muscle. These drugs, which include losartin and valsartan, are also orally active. 

More direct evidence of noradrenergic effects comes from studies using the a2 antagonist, yohimbine. a2 adrenergic receptors are known to be present on the cell bodies and terminals of norepinephrine neurons,... 

There is evidence that y-aminobutyric acid A receptors may be modified during SE and become less responsive to endogenous agonists and antagonists. Two phases of GCSE have been identified. During phase I, each seizure produces marked increases in plasma epinephrine, norepinephrine, and steroid concentrations that may cause hypertension, tachycardia, and cardiac arrhythmias. Muscle contractions and hypoxia can cause acidosis, and hypotension, shock, rhabdomyolysis, secondary hyperkalemia, and acute tubular necrosis may ensue. 

Milnacipran is currently available for use as an antidepressant in several countries outside the U.S. It is also under clinical development to assess its potential role in the treatment of fibromyalgia syndrome [62,63]. In a rat model of neuropathic pain, milnacipran, administered intrathecally, produced dose-dependent anti-allodynic effects at doses between 3 and 100 gg for up to 7h [64], The anti-allodynic effect of 30 gg of milnacipran was attenuated by intrathecal coadministration of a serotonin receptor antagonist or a norepinephrine receptor... 

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