minipress medication information
To investigate the analgesic effect, rats were intraperitoneally administered with normal saline or various doses of ROE before or after a plantar incision. To evaluate the involved mechanism, rats were intraperitoneally administered yohimbine, dexmedetomidine, prazosin, naloxone, atropine, or mecamylamine after a plantar incision; ROE was then administered intraperitoneally. The mechanical withdrawal threshold (MWT) was tested with von Frey filaments at various time points. To determine the inflammatory response, serum levels of interleukin (IL)-1β or IL-6 were measured.
minipress 1mg capsule
A controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin mesylate, a long-acting selective alpha1-adrenoceptor antagonist, was developed to enhance the pharmacokinetic profile and simplify the titration schedule by precisely controlling drug delivery rate, permitting an initial dose of 4 mg once daily, compared with standard doxazosin, which is initiated at 1 mg day-1 and titrated to a higher therapeutically effective dose. The aim of the present work was to evaluate the pharmacokinetics and bioavailability of doxazosin GITS with respect to the effect of food, age and gender, and multiple dosing. In addition, in vitro performance was assessed in conditions simulating the gastrointestinal environment.
minipress dosage forms
The properties and modulation by norepinephrine (NE) of voltage-dependent calcium currents were studied in bulbospinal neurons (n = 116) of the rostral ventrolateral medulla (RVLM) using whole cell patch-clamp techniques in neonatal rat brain stem slices. RVLM bulbospinal neurons were identified visually by their location in slices and by the presence of flourescein isothiocyanate-tagged microbeads, which were injected into the spinal cord before the experiment; RVLM neurons were filled with Lucifer yellow during recordings, and the slice was processed for detection of tyrosine hydroxylase immunoreactivity (TH-IR). Thirty-four of 42 recovered cells (81%) were positive for TH-IR, indicating that most recorded cells were C1 neurons. Bulbospinal RVLM neurons expressed a prominent high-voltage-activated (HVA) calcium current, which began to activate at -30 to -40 mV (from a holding potential of -60 or -70 mV), and peaked at approximately 0 mV (0.8 +/- 0.1 nA;mean +/- SE). HVA current comprised predominantly omega-conotoxin GVIA-sensitive, N-type and omega-agatoxin IVA-sensitive, P/Q-type components, with smaller dihydropyridine-sensitive, L-type, and residual current components. Most RVLM bulbospinal neurons (n = 44/52, including 12/14 histologically identified C1 cells) also expressed low-voltage-activated (LVA) calcium current. LVA current began to activate at approximately -60 mV (from a holding potential of -100 mV) and was nearly completely inactivated at -50 mV with a half-inactivation potential of -70 +/- 2 mV. The amplitude of LVA current at -50 mV was 78 +/- 24 pA with Ba2+ and 156 +/- 38 pA with Ca2+ as a charge carrier. NE inhibited HVA current in most bulbospinal RVLM neurons (n = 70/77) with an EC50 of 1.2 muM; NE had no effect on LVA current. Calcium current inhibition by NE was mediated by alpha2-adrenergic receptors (alpha2-ARs) as the effect was mimicked by the selective alpha2-AR agonist, UK-14,304, and blocked by idazoxan, an alpha2-AR antagonist, but unaffected by prazosin and propranolol (alpha1- and beta-AR antagonists, respectively). Most of the NE-sensitive calcium current was N- and P/Q-type. NE-induced inhibition of calcium current evoked by action potential waveforms (APWs) was significantly larger than that evoked by depolarizing steps (34 +/- 2.5 vs. 23 +/- 2.7%; P < 0.05). Although inhibition of calcium current was voltage dependent and partially relieved by strong depolarizations, when calcium currents were evoked with a 10-Hz train of APWs as a voltage command, the inhibitory effect of NE was maintained throughout the train. In conclusion, bulbospinal RVLM neurons, including C1 cells, express multiple types of calcium currents. Inhibition of HVA calcium current by NE may modulate input-output relationships and release of transmitters from C1 cells.
minipress and alcohol
The aortic pulse pressure (PP), which consists mainly of the incident wave and the reflected wave, has emerged as an important property of systemic blood vessels underlying the pathophysiology of cardiovascular disease. To determine the role of sympathetic nerve activity on the aortic PP response during dynamic exercise, we evaluated aortic hemodynamics during the right-leg knee-extension (40 and 60 % of maximal voluntary contraction) in six young adults with and without the systemic α1-adrenergic receptor blockade using prazosin (1 mg/20 kg body weight). The use of prazosin attenuated the exercise-induced increase in aortic PP (P < 0.05) but not in radial arterial PP. The amplitude of the reflected waves (via augmentation index) significantly decreased with the exercise and decreased more with the use of prazosin. These results suggest that during dynamic exercise the α1-adrenergic-mediated vasoconstrictor tone of the peripheral resistance vessels is manifestly involved in the magnitude of the reflected wave and the modulation of the aortic PP responses.
minipress 6 mg
Pheochromocytoma is associated with intense physiologic effects of alpha- and beta-adrenergic stimulation from catecholamine secretion. Perioperative management for these patients includes alpha-adrenergic receptor blockade, intravascular volume replacement, and, if necessary, beta-adrenergic receptor blockade. Significant perioperative changes in preload and afterload, fluid status, heart rate and rhythm, and inotropy can occur and may be contrary to anesthetic management goals for patients with certain conditions of congenital heart disease. We report the perioperative management with doxazosin of a patient with single ventricle physiology and cavo-pulmonary and aorto-pulmonary lung perfusion who presented for resection of a pheochromocytoma.
minipress xl drug
Troglitazone is a thiazolidinedione used for the treatment of NIDDM and potentially for other insulin-resistant disease states. Troglitazone has recently been shown to increase cardiac output and stroke volume in human subjects. These actions are thought to be mediated by the reduction of peripheral resistance, but a potential direct effect on cardiac function has not been studied. Therefore, we investigated the direct cardiac hemodynamic effects of troglitazone in isolated perfused rat hearts. Five groups of hearts were studied. Hearts were tested under isovolumetric contraction with a constant coronary flow, and troglitazone (0.2, 0.5, and 1.0 micromol) was administered by bolus injection. Peak isovolumetric left ventricular pressure (LVPmax), peak rate of rise of LVP (dP/dt(max)), and peak rate of fall of LVP (dP/dt(min)) were significantly increased 1 min after troglitazone administration in a dose-dependent manner, while the heart rate (HR) and coronary perfusion pressure (CPP) were significantly decreased (P < 0.05). HR was then fixed by pacing and/or CPP was fixed with nitroprusside to eliminate any effect of the two variables on the action of troglitazone. With constant HR and/or constant CPP, the effect of troglitazone on LVPmax, dP/dt(max), and dP/dt(min) was still unchanged. In addition, the positive inotropic, positive lusitropic, and negative chronotropic actions of troglitazone were not influenced even when hearts were pretreated with prazosin, propranolol, or nifedipine. In conclusion, troglitazone has direct positive inotropic, positive lusitropic, negative chronotropic, and coronary artery dilating effects. The inotropic and chronotropic actions of troglitazone are not mediated via adrenergic receptors or calcium channels. These findings have important clinical implications for diabetic patients with congestive heart failure.
Simple and sensitive spectrophotometric methods are described for the assay of three piperazine derivatives; ketoconazole, piribedil and prazosin hydrochloride based on charge-transfer and ion-pair complexation reactions. The first method is based on the reaction of the basic drug with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) in acetonitrile. The orange-red colour formed due to the formation of charge-transfer complex showed maximum absorbance at 460 nm. The second method is based upon the interaction of the basic drug in dry chloroform with bromophenol blue (BPB) in the same solvent to produce a stable yellow ion-pair complex which absorbs at 410 nm. Beer's law was obeyed for both methods and the relative standard deviations were found to be less than 1%. The two methods can be applied to the analysis of tablets, with no evidence of interference from excipients. A more detailed investigation of the complex was made with respect to its composition, association constant and free energy change.
The effects of l-amphetamine on the spontaneous firing of central neurons of African snails (Achatina fulica Ferussac) were studied electrophysiologically. The effects of dopamine, noradrenaline, d-amphetamine, and methamphetamine on the central neurons also were tested. The l- and d-amphetamines (0.3 mM) elicited bursting firing of action potentials in the RP4 neuron of the snail, whereas dopamine (0.3 mM), noradrenaline (NE, 0.3 mM), and methamphetamine (2 mM) did not. The bursting firing of action potentials elicited by l-amphetamine was decreased if potassium-free solution, sodium-free solution, or solution containing oubain (0.1 mM), a sodium pump inhibitor, was perfused. The results suggested that l-amphetamine did, and methamphetamine did not, elicit a sodium-dependent bursting firing of action potentials of the neuron.
This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca(2+) dependent.
Four pharmacons were tested on an acute portal pressure lowering effect in an experimental animal model with 25 normal and 25 rats with Thioacetamide-toxic liver cirrhosis. Invasive measurements of arterial and portal pressure were made under Hexobarbital-Sodium anaesthesia during 30 minutes after pharmacon application. The portal pressure of cirrhotic rats was under basic conditions 9.5 +/- 1.5 mm Hg and significant higher as in normal animals (5.3 +/- 0.9 mm Hg, p less than 0.01). After 10 mg/kg body mass Propranolol the portal pressure decreased in both animal groups small but not significantly over the whole measurement time. 1 mg/kg Verapamil lowered arterial middle pressure significantly, but increased portal pressure at all 15-20% in both animal groups. Application of 0.1 mg/kg Prazosin decreased the arterial middle pressure at all 5-15% and the portal pressure at all 20-30% in both study groups (both significantly). For Canrenoat-Potassium (20 mg/kg) no clear effect could by evaluated on portal pressure. The model of Thioacetamide-toxic cirrhosis of the rat offers conditions like cirrhosis in human medicine in order to study the effects of portal pressure lowering pharmacons. Propranolol and Prazosin decrease portal pressure and should by further investigated.
These results suggest that presynaptic or central alpha2-adrenoceptor function, or both, is specifically impaired after 9 weeks of a high-fat diet. These modifications may account for the development of arterial hypertension in this model.
minipress drug information
To evaluate the effect of electroacupuncture (EA) on symptomatic benign prostatic hyperplasia (BPH).
minipress 2 mg
Antagonism of alpha 1-adrenoceptor-mediated vascular contraction by urapidil was examined in helical strips of femoral and mesenteric arteries isolated from 13-week-old Aoki spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats, since this agent has antihypertensive effect through antagonizing peripheral alpha-adrenoceptors. Schild plot analyses clearly demonstrated the existence of only alpha 1-adrenoceptors in these arteries from both strains. Therefore, it is possible to demonstrate alpha 1-adrenoceptor blocking effects of nonselective alpha-adrenoceptor antagonists as well as selective alpha 1-adrenoceptor antagonists. Urapidil antagonized the alpha 1-adrenoceptor-mediated vascular contraction in a competitive fashion. The pA2 value for urapidil against alpha 1-adrenoceptors was not significantly different between SHR and WKY rats. The addition of 10(-5) M norepinephrine (NE) produced a sustained contraction in a SHR femoral artery, whereas in a WKY rat femoral artery this agonist produced a transient contraction followed by a sustained relaxation. Urapidil elicited a dose-dependent relaxation with a IC50 value of 6.50 in the SHR femoral artery precontracted with NE. In the presence of 3 x 10(-7) M timolol, a beta-adrenoceptor antagonist, femoral arteries from both strains exhibited similar magnitude of contraction in response to the stimulation with 10(-5) M NE. Under these conditions, urapidil elicited a similar extent of relaxation between SHR and WKY rats. On the other hand, the addition of 10(-5) M NE produced a sustained contraction in mesenteric arteries from both SHR and WKY rats. The contraction expressed as a ratio to the maximum developed by KCl depolarization was significantly greater in SHR than in WKY rats. In these arteries, the relaxing effect of urapidil was more evident in SHR than in WKY rats. Contractile responses to NE and relaxing effects of urapidil were not affected by timolol. These results suggest that urapidil effectively antagonized enhanced alpha 1-adrenoceptor responses seen in SHR arteries.
minipress overdose symptoms
The affinity of 5-methyl-urapidil for alpha 1-adrenoceptors was determined from the inhibition of [3H]prazosin binding on membrane of different rat tissues. In hippocampus, vas deferens and heart 5-methyl-urapidil displaced [3H]prazosin in a biphasic manner with mean pKI values between 9.1 and 9.4 for the high-affinity site and 7.2 to 7.8 for the low-affinity site. Only the low affinity site was found in spleen and liver. At present, 5-methyl-urapidil is the antagonist which most clearly discriminates between alpha 1-adrenoceptor subtypes.
Evoked noradrenaline release was monitored every 1 s in vivo from the hypothalamic paraventricular nucleus by differential pulse amperometry at +105 mV combined with carbon fiber electrodes. Noradrenaline release was evoked by electrical stimulations of the ventrolateral medulla for 20s every 10 min at a physiological frequency (3-20 Hz) (see accompanying paper). The evoked noradrenaline release was dose-dependently attenuated by clonidine (10-100 micrograms/kg, i.v.) and strongly enhanced by alpha-2 antagonists: yohimbine (2 mg/kg), piperoxane (2 mg/kg) and idazoxan (0.05-1 mg/kg). Moreover, the effect of clonidine (50 micrograms/kg) was prevented by yohimbine (5 mg/kg) or idazoxan (1 mg/kg). Haloperidol (50 micrograms/kg) or propranolol (10 mg/kg) did not affect evoked noradrenaline release while prazosin (0.05-1 mg/kg) induced a moderate increase. However, prazosin did not prevent the effect of clonidine (50 micrograms/kg). Reserpine (5 mg/kg) pretreatment for 1 h induced a pronounced decrease in the evoked noradrenaline release and abolished the effect of yohimbine (2 mg/kg). Pretreatment by desipramine 30 min before injection abolished the effect of clonidine (50 micrograms/kg) but not of yohimbine (2 mg/kg). The amplitude of the yohimbine (2 mg/kg) effect depended on the frequency of the stimulation: it was maximal between 3 and 7 Hz and gradually declined from 10 to 20 Hz. These results show that noradrenaline release is presynaptically controlled by an alpha-2 adrenoreceptor and suggest that, in physiological conditions, endogenous extracellular noradrenaline inhibits its own phasic release. In conclusion, noradrenergic terminals act as a high pass filter which converts impulse flow into noradrenaline release and the features of this filter are modulated by extracellular noradrenaline via an alpha-2 adrenoreceptor.
minipress tablets dose
The noradrenalin-evoked production of [3H]inositol phosphates in mouse striatal astrocytes in primary culture appeared to be the result of the combined stimulation of alpha 1- and alpha 2-adrenergic receptors. Indeed, the noradrenalin (100 microM) response was only partially reproduced by a maximally effective concentration of methoxamine (100 microM), a selective agonist of alpha 1-adrenergic receptors. In addition, the noradrenalin (100 microM)-induced production of [3H]inositol phosphates, which was completely suppressed by the alpha 1-adrenergic antagonist prazosin (1 microM), was also partially inhibited by yohimbine, a selective antagonist of alpha 2-adrenoceptors (maximum inhibition = -57 +/- 11%, measured in the presence of 10 microM yohimbine; six experiments). Finally, UK14.304, a selective alpha 2-adrenergic agonist that was ineffective alone, enhanced the methoxamine-evoked production of [3H] inositol phosphates (EC50 = 86 +/- 21 nM; three experiments). These results suggest that the stimulation of alpha 1-adrenergic receptors is required for the alpha 2-adrenergic receptor-mediated enhancement of phospholipase C activity. The increased production of [3H]inositol phosphates resulting from the stimulation of alpha 2-adrenergic receptors involved pertussis toxin-sensitive G proteins (Gi/o) and depended on extracellular calcium. As shown using the fluorescent dye indo-1, noradrenalin (100 microM) induced a long-lasting increase in cytosolic calcium in striatal astrocytes. Moreover, noradrenalin (100 microM) stimulated [3H]arachidonic acid release from these cells. These two latter responses may result from synergistic effects due to the combined stimulation of alpha 1- and alpha 2-adrenergic receptors, because they were inhibited by either prazosin (1 microM) or yohimbine (10 microM). Finally, the noradrenalin-evoked production of [3H]inositol phosphates seems to result partly from an inhibition by arachidonic acid of glutamate uptake into astrocytes, leading to the stimulation of glutamate metabotropic receptors coupled to phospholipase C. Indeed, the alpha 2-adrenergic component of the noradrenalin response was suppressed by either enzymatic removal of external glutamate or addition of 2-amino-3-phosphonopropionic acid (1 mM), an antagonist of glutamate metabotropic receptors that blocked the glutamate-evoked production of [3H]inositol phosphates in striatal astrocytes, and was reproduced by the direct application of either glutamate or an inhibitor of glutamate uptake, beta-methyl-DL-aspartic acid.
In vitro long-term facilitation (ivLTF) is a novel form of activity-independent postsynaptic enhancement of AMPA receptor function in hypoglossal (XII) motoneurons that can be induced by intermittent activation of 5-HT2 receptors. In vivo respiratory long-term facilitation (LTF) is characterized by a persistent 5-HT2 receptor-dependent increase in respiratory motor output or ventilation after episodic exposures to hypoxia in adult rats. Here, we demonstrate that ivLTF can also be induced by episodic but not continuous stimulation of alpha1-adrenergic receptors that requires protein kinase C (PKC), but not PKA (protein kinase A), activation. Additionally, we show that in vivo respiratory LTF is also alpha1-adrenergic receptor dependent. We suggest that, in vivo, concurrent episodic activation of 5-HT2 and alpha1-adrenergic receptors is necessary to produce long-lasting changes in the excitability of respiratory motoneurons, possibly involving PKC activation via the G alpha(q)-PLC (phospholipase C) signaling pathway common to both receptor subtypes. Such plasticity of XII motor output may increase upper airway muscle (innervated by XII nerve) tone and improve the likelihood that airway patency will be maintained. Elucidating the mechanism underlying LTF can be of clinical importance to the patients suffering from sleep-disordered breathing.
minipress drug class
We identified 69 men with symptomatic benign prostatic hyperplasia (BPH) who had been receiving 5 mg/day (n = 33) of finasteride or 2 to 5 mg/day (n = 14) of terazosin or no therapy ("watchful waiting") (n = 22). The three groups were compared with respect to pretreatment total serum PSA levels and post-treatment total, free, and percent free serum PSA levels.
The activation of p70(S6) kinase and JNK2 may be implicated in the development of catecholamine-induced cardiac hypertrophy in vivo.
The role of spinal mechanisms in subcutaneous (s.c.) nicotine-induced antinociception was examined in male Sprague-Dawley rats using the hot-plate and tail-flick tests. Nicotine (0.125, 0.25, 0.375 or 0.5 mg/kg s.c.) produced a dose-related inhibition of nociception in both tests. Although increasing negative geotaxis response times slightly, no significant alteration of other motor reflexes was observed with 0.375 mg/kg of s.c. nicotine. Microinjection of 7 nmol of the high-affinity choline uptake inhibitor hemicholinium-3 into the rostral ventral medulla completely inhibited the antinociception produced by 0.375 mg/kg of s.c. nicotine. Intrathecal (i.t.) injection of 61 nmol of nicotine (in 10 microliter buffer) produced no changes in hot-plate or tail-flick test response latencies. Nicotine-induced antinociception was blocked by a variety of i.t. antagonists injected 12 min before s.c. injection of 0.375 mg/kg of nicotine. In both tests, i.t. pretreatment with 0.1 mumol (in 10 microliter buffer) of scopolamine, methysergide, yohimbine, idazoxan, mecamylamine or 0.2 mumol of atropine attenuated nicotine-induced increases in test response latencies. Pretreatment with 0.1 mumol of atropine attenuated nicotine-induced increases in tail-flick test, but not in the hot-plate test. Pretreatment with 0.1 mumol of i.t. prazosin or naloxone produced no changes in nicotine-induced increases in test response latencies in either test. These data suggest that the antinociception produced by s.c. nicotine is mediated via a number of sites in the spinal cord, including alpha-2 adrenergic, serotonergic and muscarinic cholinergic.(ABSTRACT TRUNCATED AT 250 WORDS)
minipress max dose
alpha 1-Adrenoceptors (ARs) were divided into alpha 1H and alpha 1L subtypes by their different affinities for bunazosin or prazosin. alpha 1H-ARs were further subdivided into alpha 1A, alpha 1B, and alpha 1C subtypes. Therefore, this study was undertaken to determine which alpha 1-AR subtypes were involved in the activation of femoral artery preparations by alpha 1-AR agonists in spontaneously hypertensive rats (SHR). For comparison, aortic strips were also incorporated in the present study. In the presence of propranolol, deoxycorticosterone, and desipramine, norepinephrine (NE) contracted the vascular strips in a dose-dependent manner. Negative log EC50 values and maximum responses of NE-induced contraction of the SHR femoral artery were unchanged and increased, respectively, compared with those of Sprague-Dawley and Wistar-Kyoto rats (WKY). Contractile responses of the SHR aortae to NE were similar to those of the normotensive tissues. Schild plot data for alpha 1-AR antagonists indicated that alpha 1-AR subtypes mediating contraction of the aorta were homogeneous and had high affinities for bunazosin (pA2 9.4, alpha 1H subtype) and WB 4101 (pA2 9.3) and a low affinity for 5-methylurapidil (pA2 7.7). In the femoral artery, because Schild plots for bunazosin had slopes of less than 1.0, there were alpha 1H and alpha 1L subtypes. Bunazosin, at 10(-9) M, which could mask the alpha 1H subtype, yielded a Schild plot for bunazosin with a slope not different from unity and decreased the pA2 value for bunazosin (pA2 9.4 vs. 8.5).(ABSTRACT TRUNCATED AT 250 WORDS)
minipress ptsd dosage
To assess the effects of doxazosin, a selective alpha 1 adrenoceptor inhibitor, on blood pressure and urinary flow in normotensive and hypertensive (sitting diastolic blood pressure more than 90 mm Hg) men with prostatic hyperplasia (BPH).
minipress xl tablets
The results support a role of the SNS in driving the chronic visceral and somatic hypersensitivity seen in CI rats. The findings further suggest that treatments that decrease sympathetic outflow or block activation of adrenergic receptors on sensory nerves could be beneficial in the treatment of generalized pain syndromes.
minipress overdose death
Calcium antagonists blunt the constrictor effects of vasoconstrictor agents. Differences in the sensitivity of several vasoconstrictors to the constrictor effect of calcium antagonists were quantified in experiments on rats and rabbits. In rats, the dose-response curves for pressor effects to angiotensin II were shifted in parallel to the right after treatment with isradipine, but not with prazosin and dihydralazine, suggesting that the antivasoconstrictor effect of isradipine was of a specific type. Blood pressure increases elicited by angiotension II or norepinephrine (alone, or with propranolol or propranolol plus prazosin) were also measured in rabbits and, again, isradipine caused parallel shifts of the dose-response curves. Both agonists thus appear to stimulate calcium entry, at least in resistance vessels, and via the same pathway, the L-type calcium channel. However, the angiotension II pressor effects were more sensitive to isradipine than those of norepinephrine in the presence of propranolol, and even more so in the presence of propranolol plus prazosin. These results suggest subtle and as yet unexplained differences, possible related to the activity of the adenylate cyclase system, in the chain of events leading to activation of the L-channels in vivo.