prazosin extended release

BACKGROUND AND AIMS: Pre-clinical studies suggest that the simultaneous blockade of the α1b and 5HT2A receptors may be effective in reducing alcohol consumption. This study aimed to assess the efficacy and safety of prazosin (α1b blocker) and cyproheptadine (5HT2A blocker) combination in decreasing total alcohol consumption (TAC) in alcohol use disorder (AUD). DESIGN, SETTING AND PARTICIPANTS: This was a double-blind, parallel group, placebo-controlled, Phase 2, randomized clinical trial conducted in 32 addiction treatment centres in France...

The dorsal raphe nucleus (DRN) is essential for the control of food intake. Efferent projections from the DRN extend to several forebrain regions that are involved in the control of food intake. However, the neurotransmitters released in the DRN related to the control of food intake are not known. We have previously demonstrated that a tonic α1 action on DRN neurons contributes to satiety in the fed rats. In this study we investigated the participation of norepinephrine (NE) signaling in the DRN in the satiety response...

BACKGROUND: Serotonin and norepinephrine reuptake inhibitors are effective first-line agents for the treatment of posttraumatic stress disorder (PTSD), but treatment is associated with a range of side effects that limit treatment adherence. Prazosin, an α1-noradrenergic antagonist with a half-life of roughly 2-3 hours, has shown promise in the treatment of sleep disturbance and nightmares. Doxazosin extended release (XL) is also an α1-noradrenergic antagonist but with a half-life of approximately 15-19 hours...

Opioids represent effective drugs for the relief of pain, yet chronic opioid use often leads to a state of increased sensitivity to pain that is exacerbated during withdrawal. A sensitization of pain-related negative affect has been hypothesized to closely interact with addiction mechanisms. Neuro-adaptive changes occur as a consequence of excessive opioid exposure, including a recruitment of corticotropin-releasing factor (CRF) and norepinephrine (NE) brain stress systems. To better understand the mechanisms underlying the transition to dependence, we determined the effects of functional antagonism within these two systems on hyperalgesia-like behavior during heroin withdrawal utilizing models of both acute and chronic dependence...

A simple, selective, and sensitive high performance liquid chromatography (HPLC) procedure has been developed for determination of trazodone in human plasma. Prazosin was employed as the internal standard (IS). Sample preparation involved liquid-liquid extraction by methyl tert-butyl ether after alkalinization with ammonia. The HPLC separation was performed on a CAPCELL PAK SCX column (250mm×4.6mm, 5.0μm, Shiseido, Japan) with a mobile phase of acetonitrile/80mmol/L ammonium phosphate (pH adjusted to 6.0) (60:40, v/v) at a flow rate of 1...

A novel three-layered tablet consisting of a water-soluble mid-layer and two barrier layers with swellable polymers was investigated to develop a preferable once-a-day formulation containing terazosin HCl as a hydrophilic model drug. When the tablet was exposed to a release medium, the medium quickly permeated to the mid-layer and the two barrier layers swelled surrounding the mid-layer rapidly. It facilitated the tablet to absorb a lot of water compared with monolithic matrix. Moreover, formation of a lot of pores in the tablet during dissolution could be observed, suggesting significant water absorption in the inner matrix and swollen polymers of the tablet...

Interpenetrating network (IPN) hydrogel membranes of sodium alginate (SA) and poly(vinyl alcohol) (PVA) were prepared by solvent casting method for transdermal delivery of an anti-hypertensive drug, prazosin hydrochloride. The prepared membranes were thin, flexible and smooth. The X-ray diffraction studies indicated the amorphous dispersion of drug in the membranes. Differential scanning calorimetric analysis confirmed the IPN formation and suggests that the membrane stiffness increases with increased concentration of glutaraldehyde (GA) in the membranes...

Eleven subjects aged <20 yr with histologically proven pheochromocytoma between 1987 and 2006 were analyzed. Family history was present in 18%. In 2 patients, pheochromocytoma was part of VHL and in one it was associated with MEN 2. Twenty four hour urine VMA level was elevated in 100% and metanephrine level in 73%. CT/ MRI were showing the tumor in all. Prazosin extended release tablets (maximum 30 mg/day) were used in 73% and doxazosin (maximum 12 mg/ day) in 27%. Intraoperative BP fluctuations were seen in 27%...

BACKGROUND: Extended-release (ER) alfuzosin hydrochloride is the most recently approved alpha-adrenergic receptor antagonist (AARA) for the management of symptomatic benign prostatic hyperplasia (BPH). Although new to the United States, alfuzosin has been available in immediate-release (IR) and sustained-release (SR) formulations in other countries for many years. OBJECTIVE: This article reviews data on the pharmacodynamics, pharmacokinetics, efficacy, tolerability, drug-interaction potential, and dosing of alfuzosin ER...

Though drug discrimination techniques have proven invaluable in characterizing the interoceptive properties of drugs of abuse, antipsychotics and anxiolytics, with the exception of some fragmentary data with tricyclic agents, surprisingly few studies have been undertaken with antidepressants. Nevertheless, the preferential dopamine (DA) reuptake inhibitor, bupropion, elicits a robust discriminative stimulus in rodents. Moreover, in rats trained on a two-lever FR-10 schedule for food reward, the selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram, and the noradrenaline (NA) reuptake inhibitor (NARI), reboxetine, elicit discriminative stimuli at doses that selectively elevate extracellular levels of 5-HT and NA, respectively...

In the rat, postsynaptic 5-hydroxytryptamine2A receptors medial prefrontal cortex control the activity of the serotonergic system through changes in the activity of pyramidal neurons projecting to the dorsal raphe nucleus. Here we extend these observations to mouse brain. The prefrontal cortex expresses abundant 5- hydroxytryptamine2A receptors, as assessed by immunohistochemistry, Western blots and in situ hybridization procedures. The application of the 5-hydroxytryptamine2A/2C agonist DOI (100 microm) by reverse dialysis in the medial prefrontal cortex doubled the local release of 5-hydroxytryptamine...

OBJECTIVE: The in vitro interaction between sympathetic nerves and basal nitric oxide release was studied in a resistance artery, since these interact powerfully in large vessels. METHODS: The pharmacological interaction between L-NAME and vasoconstriction to field stimulation of sympathetic nerves or exogenous norepinephrine was studied in rabbit cutaneous resistance arteries in wire myographs. RESULTS: Relaxation of norepinephrine-induced tone by acetylcholine, but not sodium nitroprusside, was blocked by N omega-nitro-L-arginine methyl ester (L-NAME: 100 microM), indicating that the agonist-induced release of nitric oxide could oppose the vasoconstrictor effect of norepinephrine and confirming that L-NAME had no effect on endothelium-independent vasodilatation...

Neuroleptics are known to stimulate dopamine release in neostriatal terminal areas. In the present study, we have investigated by brain microdialysis in freely moving rats the effect of typical and atypical neuroleptics on dopamine transmission in the bed nucleus of stria terminalis, a dopamine terminal area belonging to the limbic system and recently assigned the so-called extended amygdala. Mean basal dialysate dopamine values were 14.3 f moles/20 microliters sample. Dopamine output in dialysates was increased dose-dependently by clozapine (max + 158%, 298%, and 461% of basal at 5, 10, and 20 mg/kg i...

The mechanism of agonist-activated arachidonate release was studied in segments of rat tail artery. Tail artery segments were prelabeled with [3H]arachidonate and then stimulated with norepinephrine (NE), and the radioactivity of the extracellular medium was determined. NE stimulated arachidonate release from the tissue without increasing arachidonic acid levels within cellular cytosol or crude membranes. About 90% of the extracellular radioactivity was shown to be unmetabolized arachidonate by TLC. Arachidonic acid release was not inhibited by the removal of the endothelium from the artery...

Bunazosin (CAS 52712-76-2), a quinazoline derivative, selectively blocks alpha1-receptors. In addition to its potent antihypertensive property, beneficial effects on lipid metabolism, glucose metabolism, vascular smooth muscle cell proliferation, it can be used in the presence of concomitant diseases, such as obstructive bronchitis, chronic renal insufficiency, peripheral arterial occlusive disease, and diabetes mellitus. In its extended-release formulation (bunazosin retard), it is generally a well-tolerated alpha1-blocker when compared to other agents in its class...

Parallel measurements of plasma alpha-melanotropin-like immunoreactivity (alpha-MSH-LI) and beta-endorphin-like immunoreactivity (beta-END-LI) were used to examine the differential adrenergic control of beta-END secretion from the anterior lobe (AL) versus the intermediate lobe (IL) of the rat pituitary gland in vivo. Changes in plasma alpha-MSH-LI levels after treatment with various adrenergic agents served as an index of the secretion of the peptides by the IL. Secretion of beta-END-LI from the AL in vivo was evaluated using the selective inhibitory effects of dexamethasone on AL release...

Felodipine is a dihydropyridine calcium antagonist which selectively relaxes vascular smooth muscle. By acting at peripheral arterioles, it lowers systemic vascular resistance and thereby produces substantial decreases in blood pressure and increases in cardiac output. Felodipine is indicated for the management of hypertension, and in patients with mild to moderate disease felodipine monotherapy markedly lowers blood pressure. It proved as effective as atenolol, and equivalent to hydrochlorothiazide, either with or without amiloride, in terms of antihypertensive activity...

The effects of pressure-applied noradrenaline (NA) on the activity of neurosecretory cells of the supraoptic nucleus (SON) were examined in anaesthetized male rats. Spontaneously active, antidromically identified neurosecretory cells were classified as vasopressin (VP)-secreting on the basis of activity patterns and responsiveness to baroreceptor activation. The probability of encountering VP units was enhanced by confining electrode penetrations to the caudal aspect of the SON. Application of low concentrations of NA (50-150 microM) excited 75% of putative VP neurones tested (n = 45), while very high concentrations (1-100 mM) were inhibitory (79%, n tested = 14)...

Previous researches demonstrated that in the rat vas deferens the effects of noradrenaline released by tyramine were more easily affected than those induced by exogenous noradrenaline by the non selective alpha-blockers, phentolamine and dihydroergocristine. The investigation has now been extended to the effects of selective alpha-blockers, prazosin and yohimbine with the aim to see whether the major sensitivity of tyramine to alpha-blockade correlates with the type of receptor activated. The results obtained with the two antagonists which selectively block alpha 1 and alpha 2 receptors strongly resemble each other and those previously obtained with the non selective alpha-adrenoceptor blockers...

Previous studies had suggested that norepinephrine (NE) and its precursors dopamine (DA) and L-DOPA acted similarly on iodine metabolism of isolated thyroid cells. Present studies indicate that this similarity extends to the inhibition by catecholamines of TSH-stimulated T4 release by mouse thyroids incubated in vitro. DA (5 X 10(-4) M), like NE, shown previously, inhibits TSH-stimulated T4 release. This inhibition was reversed by the alpha-blockers phentolamine, prazosin, and yohimbine, but not by the beta-blocker L-propranolol...