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PubMed1996

Comparison of the effects of clonidine on tyramine- and methoxamine-evoked mydriasis in man.

1. It has been reported previously that clonidine can potentiate tyramine-evoked mydriasis on the pain-free side of cluster headache patients. We examined whether a single oral dose of clonidine (200 micrograms) can also potentiate tyramine-evoked mydriasis in healthy subjects, using mydriasis to methoxamine, a directly acting sympathomimetic amine, as a control. 2. Eight healthy male volunteers participated in four weekly sessions. In the first two sessions (Experiment 1) the effect of clonidine or placebo on the mydriasis to tyramine hydrochloride eyedrops (75 mM; 2 x 10 microliters), and in the last two sessions (Experiment 2) the effect of clonidine or placebo on the mydriasis to methoxamine hydrochloride eyedrops (20 mM; 2 x 10 microliters) was examined. In both experiments subjects were allocated to drugs and sessions according to a double-blind balanced design. In both experiments, pupil diameter of both the treated and the untreated eyes was recorded in standard ambient light and in the dark, before, and 2 h after clonidine/placebo, via binocular infrared television pupillometry. Salivation (dental roll technique), systolic and diastolic blood pressure (sitting), heart rate, and self-ratings of mood and feelings (visual analogue scales), were also measured before, and 2 h after the ingestion of clonidine or placebo. 3. Both tyramine and methoxamine produced a significant mydriasis, which was more prominent in the light condition (change in resting pupil size; mm +/- s.e.mean: tyramine/light 1.05 +/- 0.28; tyramine/dark: 0.73 +/- 0.15; methoxamine/light: 1.65 +/- 0.28; methoxamine/dark: 0.85 +/- 0.15). Clonidine produced a significant miosis in the untreated eye which was more prominent in the light condition (change in resting pupil size; mm +/- s.e.mean: Experiment 1, light: -1.34 +/- 0.19; Experiment 1, dark: -0.46 +/- 0.1; Experiment 2, light -0.97 +/- 0.18; Experiment 2, dark: -0.29 +/- 0.17). Clonidine had no significant effect on either tyramine- or methoxamine-evoked mydriasis. 4. In agreement with previous reports, clonidine significantly reduced salivation (g, mean +/- s.e.mean; Experiment 1: -0.84 +/- 0.22; Experiment 2: -0.55 +/- 0.11), systolic blood pressure (mm Hg; Experiment 1: -17.5 +/- 3.76; Experiment 2: -23.38 +/- 4.67), diastolic blood pressure (mm Hg; Experiment 2: -12.38 +/- 2.05), alertness (mm; Experiment 2: -24.19 +/- 5.40), and anxiety (mm; Experiment 1: -13.82 +/- 4.60), indicating the presence of pharmacodynamically effective tissue levels of the drug. 5. These results show that a single oral dose (200 micrograms) of clonidine causes significant miosis in human subjects, and fails to potentiate tyramine-evoked mydriasis. This indicates that the pupil on the asymptomatic side of cluster headache patients is affected differently from the pupils of healthy volunteers by tyramine and/or clonidine.

Adolescent↗
PubMed1999

Comparison of the effects of venlafaxine, desipramine, and paroxetine on noradrenaline- and methoxamine-evoked constriction of the dorsal hand vein.

AIMS: To examine whether the antidepressant venlafaxine, a novel serotonin-noradrenaline re-uptake inhibitor (SNRI), can modify alpha-adrenoceptor-mediated venoconstriction in man. The effects of venlafaxine were compared with those of desipramine, a tricyclic antidepressant with noradrenaline uptake inhibiting properties, and paroxetine, a selective serotonin re-uptake inhibitor (SSRI), on noradrenaline-and methoxamine-evoked venoconstriction using the dorsal hand vein compliance technique. METHODS: Fifteen healthy male volunteers participated in five weekly experimental sessions. Each session was associated with a clinically effective dose of an antidepressant or placebo. The following oral dosages were used: venlafaxine 75 mg, venlafaxine 150 mg, desipramine 100 mg, paroxetine 20 mg, or placebo. A double-blind, cross-over, balanced design was used. In each session, dose-response curves to both locally infused noradrenaline acid tartrate (0.1-33.33 ng min-1 ) and methoxamine hydrochloride (0.5-121.5 microg min-1 ) were constructed. Systolic and diastolic blood pressure and pulse rate were measured in the supine and erect positions. Salivation was measured by the dental roll technique. RESULTS: Venlafaxine 150 mg and desipramine 100 mg potentiated the venoconstrictor response to noradrenaline (anova of log ED50s: P<0.01; individual comparisons: venlafaxine 150 mg vs placebo: P<0.005; mean difference, 95% CI: -0. 49 (-0.81, -0.17); desipramine 100 mg vs placebo: P<0.005; mean difference, 95% CI: -0.34 (-0.60, -0.09) without affecting the response to methoxamine. Neither paroxetine nor placebo had any effects on the venoconstrictor responses. Both doses of venlafaxine increased systolic blood pressure (supine and erect) and venlafaxine 150 mg increased diastolic blood pressure (supine) (anova, P<0.05). Desipramine increased heart rate (P<0.05). Desipramine and both doses of venlafaxine reduced salivation (P<0.025). CONCLUSIONS: These results show that, similarly to desipramine 100 mg, venlafaxine 150 mg can potentiate venoconstrictor responses to noradrenaline, consistent with venlafaxine's ability to block noradrenaline uptake in man. The importance of noradrenaline uptake blockade in these observations is confirmed by the lack of effect of the antidepressants on methoxamine-evoked venoconstriction and the failure of paroxetine to modify noradrenaline-evoked venoconstriction.

Adrenergic alpha-Agonists↗
PubMed1997

Lack of delayed effects of amphetamine, methoxamine, and prazosin (adrenergic drugs) on behavioral outcome after lateral fluid percussion brain injury in the rat.

This study examined the delayed effects of the administration of d-amphetamine, methoxamine (an alpha1-adrenergic receptor agonist), and prazosin (an alpha1-adrenergic receptor antagonist) on the behavioral outcome of lateral fluid-percussion (FP) brain injury. Rats trained to perform a beam-walking task were subjected to brain injury of moderate severity (2.1 to 2.2 atm). Twenty-four hours after injury, rats were treated with amphetamine, methoxamine, or prazosin at two or three different dose levels. Amphetamine-treated animals displayed no significant improvement in beam-walking ability either during or after drug intoxication (from days 3 to 5 after brain injury). Similarly, neither methoxamine nor prazosin significantly affected beam-walking ability during or after drug intoxication. Neither amphetamine treatment at three different doses nor treatment with methoxamine or prazosin at two different doses affected the spatial learning disabilities of brain-injured animals. These results suggest that (1) unlike amphetamine administration after sensorimotor cortex (SMC) ablation or contusion brain injury models, amphetamine administration at 24 h after concussive FP brain injury does not improve beam-walking performance; (2) unlike amphetamine administration 10 min after concussive FP brain injury amphetamine administration 24 h after injury does not improve cognitive function; and (3) unlike prazosin administration after SMC ablation brain injury, prazosin administration 24 h after concussive FP brain injury does not effect beam-walking performance.

Amphetamine↗
PubMed1984

Effects of methoxamine and alpha-adrenoceptor antagonists, prazosin and yohimbine, on the sleep-wake cycle of the rat.

A study was carried out on the effects of methoxamine, prazosin, and yohimbine on the sleep-wake cycle in rats prepared for chronic sleep recordings. Methoxamine (4-8 mg/kg), an alpha 1-adrenoceptor agonist, induced a dose-related increase in wakefulness (W) and a decrease in slow-wave sleep (SWS) and REM sleep (REMS). Prazosin (0.125-1 mg/kg), which selectively blocks alpha 1-adrenoceptors, modified only slightly the amount of time spent in W and SWS, and consistently decreased REMS values. Prazosin (0.5 mg/kg) reversed the effects of methoxamine, decreasing W and increasing sleep. Yohimbine (3 mg/kg), which blocks alpha 2-adrenoceptors, augmented W and diminished sleep. Methoxamine (4 mg/kg) in animals pretreated with yohimbine (3 mg/kg) induced a further decrease of SWS and REMS and an increase of W. Thus, pharmacological activation of alpha 1- or blocking of alpha 2-adrenoceptors appears to decrease sleep and increase W. Further, blocking of alpha 1-adrenoceptors decreases REMS. Rapid eye movement sleep depression by the alpha 1-agonist or the alpha 1-antagonist is tentatively ascribed to a critical change in noradrenergic transmission in the brain.

Animals↗
PubMed1984

The action of prazosin and propylene glycol on methoxamine-induced bronchoconstriction in asthmatic subjects.

The effect of 1 mg inhaled prazosin on bronchoconstriction induced by methoxamine was investigated in seven asthmatic subjects. Prazosin caused significant inhibition of the methoxamine-induced bronchoconstriction in six of the seven patients. These findings suggest that methoxamine produces bronchoconstriction in asthmatic subjects via stimulation of alpha-adrenoceptors. In previous studies propylene glycol has been used as a vehicle for delivery of prazosin. This substance was found to cause significant inhibition of methoxamine effects and to shift the dose response curve to histamine to the right in four of seven patients.

Adult↗
PubMed1982

Myocardial responses to alpha-adrenoceptor stimulation with methoxamine hydrochloride in lambs.

This study was undertaken to evaluate the effects of methoxamine on left ventricular performance, coronary blood flow (CBF), and myocardial oxygen consumption (MVO2) in lambs. Measurement of maximum rate of rise of left ventricular pressure (LV dP/dtmax), left ventricular end-diastolic pressure (LVEDP), CBF, and MVO2 were made in nine lambs using a hemodynamically controlled preparation. The lambs were given atropine sulfate (1 mg), tetraethylammonium chloride (100 mg), and practolol (4 mg/kg) to provide parasympathetic, ganglionic, and beta-adrenergic blockades. Aortic pressure and blood flow and heart rate were held constant in each lamb. Dose-related increases in LV dP/dtmax and decreases in LVEDP were observed after progressively larger doses of methoxamine ranging from 0.4 to 6.0 mg/kg were given. These positive inotropic responses were eliminated by giving phentolamine (2 mg/kg). CBF, myocardial O2 extraction, and MVO2 did not change significantly. A positive inotropic action of methoxamine was also demonstrated in five additional animals by obtaining ventricular function curves. Initially the mean stroke volume at LVEDP 10 cmH2O (SV10) was 4.11 +/- 0.16 (SE) ml. This value increased to 5.09 +/- 0.28 ml after methoxamine (P less than 0.01). After phentolamine, SV 10 fell to 4.37 +/- 0.08 ml (P less than 0.05). These observations support the hypothesis that alpha-adrenergic receptors are present and mediate a substantial positive inotropic action on neonatal lamb myocardium.

Animals↗
PubMed1995

A randomized, double-blind comparison of methoxamine and epinephrine in human cardiopulmonary arrest.

The beneficial effect of epinephrine has been attributed to its alpha-adrenergic properties. The present study was designed to compare the effects of epinephrine and methoxamine in witnessed cardiac arrests. Consecutive, witnessed cardiac-arrest victims presenting to the emergency room or from the inpatient population of our institution were enrolled in this study. Patients were randomized to receive either epinephrine (2 mg bolus followed by 2 mg every 4 min) or methoxamine (40 mg bolus followed after 4 min by 40 mg) in a blind design. Patients were followed prospectively for survival and neurologic outcome. A total of 199 patients were randomized into the study, but 54 had to be retrospectively dropped from analysis for failure to comply with the study protocol. Of the 145 patients remaining, 77 received methoxamine (M) and 68 epinephrine (E). There was no difference in rate of successful resuscitation (42% versus 53%, M versus E, respectively), or in neurologic outcome as measured by the Glasgow-Pittsburgh Coma Score (GPCS). This study failed to demonstrate any difference in the rate of initial resuscitation, survival to discharge from the hospital, or neurologic status with methoxamine as opposed to epinephrine in the setting of cardiac arrest.

Adult↗
PubMed1991

The alpha 1-adrenergic agonist methoxamine and the "loop" diuretic frusemide reduce nasal potential difference.

Pretreatment by inhalation with the alpha 1-adrenergic agonist methoxamine and the "loop" diuretic frusemide reduces the bronchial response to certain airway challenges in asthma. To test whether these drugs may act by altering airway epithelial ion and water transport, their effect on nasal potential difference (PD) when applied topically in eight normal volunteers was measured. For comparison, the effect of the Na(+)-channel blocking drug amiloride and the beta 2-adrenergic agonist salbutamol was also tested. Both methoxamine and frusemide significantly reduced PD: at the highest concentration given (10(-3) mol.l-1), there was a mean drop in PD from baseline of 39.5% following methoxamine treatment (p less than 0.05) and a mean drop of 30.2% following frusemide (p less than 0.05). Neither drug was as effective as amiloride, which caused a mean drop in PD of 27.5% from baseline at 10(-6) mol.l-1 and a drop of 71.6% at 10(-3) mol.l-1 (p less than 0.01 for each concentration). Salbutamol had no significant effect on PD (p greater than 0.05). We conclude that methoxamine and frusemide may derive their protective effect on some bronchial challenge, at least in part, from their effect on airway epithelial ion flux.

Adult↗
PubMed1977

Effects of methoxamine on the coronary circulation during cardiopulmonary bypass.

Effects of perfusion pressure augmentation with methoxamine on transmural distribution and adequacy of coronary blood flow during cardiopulmonary bypass were investigated. Flow in normal, nonworking canine hearts was measured with tracer microspheres and electromagnetic flow probes while heart rate, myocardial oxygen consumption, left ventricular contractility and epicardial ST-segment stability were monitored. Measurements during normotensive cardiopulmonary bypass were compared with values during intraoperative hypotension and subsequent normotension achieved following methoxamine infusion. Total and regional coronary blood flow returned to levels not different from normotensive controls after methoxamine infusion with a redistribution of flow to the subendocardium. We conclude that elevating perfusion pressure during cardiopulmonary bypass with methoxamine infusion increases total coronary and subendocardial blood flow by means of peripheral and selective subepicardial alpha adrenergic vasoconstriction.

Animals↗
PubMed2005

Intra-anal and rectal application of L-erythro methoxamine gel increases anal resting pressure in healthy volunteers.

BACKGROUND: This study examined the effect of a single local application of L-erythro methoxamine, an alpha(1)-adrenoceptor agonist, on mean anal resting pressure (MARP) and cardiovascular variables in healthy volunteers. METHODS: L-Erythro methoxamine gel was administered in a single-blind manner; 0.3-3 per cent gels were applied perianally (n = 12), 1-3 per cent gels intra-anally (n = 16) and 1 per cent gel rectally (n = 8). MARP, systolic blood pressure, diastolic blood pressure and pulse rate were measured before application and for up to 6 h afterwards. Blood samples were taken to estimate plasma drug levels. RESULTS: Perianal gel produced no increase in MARP. Intra-anal 1 per cent and 3 per cent gel produced a significant rapid rise in MARP for 4 and 5 h respectively after application (P = 0.012 and P = 0.017 respectively). Rectal 1 per cent gel increased MARP for 2 h after application (P = 0.036). Intra-anal gel resulted in an increase in systolic blood pressure (1 per cent gel at 2 h, P = 0.042; 3 per cent gel at 4 h, P = 0.017). One per cent intra-anal and rectal gels caused a decrease in the pulse rate for 2 h after application (P = 0.012 and P = 0.018 respectively). Six subjects complained of nausea and three of headache after gel application. CONCLUSION: Intra-anal and rectal gel produced a sustained rise in MARP with rapid onset in volunteers. This raises the possibility of a therapeutic application for L-erythro methoxamine in patients with passive incontinence and internal anal sphincter dysfunction.

Administration, Rectal↗
PubMed1976

Effects of midodrine, ST 1059, methoxamine and glycine on spontaneously beating guinea-pig atria.

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.

Adrenergic alpha-Agonists↗
PubMed1978

Effect of propranolol and nitroglycerin plus methoxamine on transmural creatine kinase activity after acute coronary occlusion.

Transmural creatine kinase activity was determined 5 hours after acute occlusion of the left anterior descending coronary artery in 27 open chest anesthetized dogs. In seven dogs, propranolol, 2 mg/kg, was given intravenously over a 10 minute period 10 minutes after occlusion. In 10 dogs, nitroglycerin, 300 microgram/min, was infused intravenously for 1 hour 10 minutes after occlusion. Methoxamine, 300 to 500 microgram, was administered to return blood pressure and heart rate to prenitroglycerin levels. In untreated dogs, there was a distinct transmural gradient of creatine kinase activity in the ischemic region from subepicardium to subendocardium: nonischemic subepicardium 1,187 +/- 50 international units (IU)/g versus ischemic subepicardium 1,054 +/- 46 IU/g and nonischemic subendocardium 1,170 +/- 53 IU/g versus ischemic subendocard;um 766 +/- 42 IU/g, respectively. Administration of propranolol did not affect the transmural creatine kinase gradient after 5 hours of occlusion. In contrast, nitroglycerin plus methoxamine significantly (P less than 0.05) decreased subendocardial creatine kinase depletion after 5 hours of occlusion (776 +/- 42 versus 978 +/- 47 IU/g). These findings demonstrate the unique capability of nitroglycerin plus methoxamine to protect the subendocardium during ischemic insult.

Acute Disease↗
PubMed1987

Pre- and postjunctional alpha-adrenoceptor-mediated effects of prazosin, methoxamine and 6-fluoronoradrenaline in blood-perfused canine skeletal muscle in situ.

Pre- and postjunctional effects of the alpha 1-selective adrenoceptor antagonist prazosin and the alpha 1- and alpha 2-selective adrenoceptor agonists methoxamine and 6-fluoronoradrenaline, respectively, were studied in skeletal muscle in situ. Prazosin reduced the vasoconstriction and enhanced the overflow of endogenous noradrenaline elicited by sympathetic nerve stimulation (1-4 Hz, 2 min); the threshold concentration was 10-100 times lower for postjunctional than for prejunctional alpha-adrenoceptor blockade. The enhancement of noradrenaline overflow by prazosin was not inversely frequency-dependent, as shown elsewhere for alpha 2-adrenoceptor antagonists. Thus, different mechanisms may be involved. Inhibition of prostaglandin synthesis by diclofenac did not alter the stimulation-evoked noradrenaline overflow, indicating a minor importance of prostaglandin-mediated transjunctional mechanisms in the modulation of noradrenaline overflow. Methoxamine and 6-fluoronoradrenaline elevated the basal vascular tone and, at higher concentrations, reduced the stimulation-evoked noradrenaline overflow. Methoxamine was 20 times more selective than 6-fluoronoradrenaline for postjunctional receptors. Our results are compatible with a pre- and postjunctional localization of alpha 2-adrenoceptors and a predominantly, but not exclusively, postjunctional localization of alpha 1-adrenoceptors. The postjunctional selectivity for prazosin was less marked than previously reported from in vitro studies. Hence, care should be taken when extrapolating in vitro findings to the more complex in vivo situation.

Animals↗
PubMed1992

Microinjection of the alpha 1-agonist methoxamine into the paraventricular hypothalamus induces anorexia in rats.

Adrenergic receptors within the paraventricular hypothalamus (PVN) play a prominent role in the control of food intake: stimulation of alpha 2-adrenoceptors induces food intake whereas stimulation of alpha 1-adrenoceptors suppresses food intake. This study further examines the role of PVN alpha 1-adrenoceptors by examining the effects on food and water intake of the alpha 1-adrenergic agonist methoxamine (100, 200, 400 nMol) microinjected into the rat paraventricular hypothalamus. Methoxamine suppressed food intake but not water intake. Doses of 100, 200, and 400 nMol methoxamine suppressed food intake by 47%, 64%, and 96%, respectively. These results further confirm the hypothesis that administration of alpha 1-agonists into the PVN acts to significantly suppress food intake; an action that is in opposition to the facilitory effects of alpha 2-adrenergic agonists on food intake.

Animals↗
PubMed1992

Effects of methoxamine and barium on 45Ca2+ fluxes in the rat vas deferens.

The aim of this study was to determine whether methoxamine and barium stimulate 45Ca2+ uptake or efflux in the rat vas deferens in a manner that correlates with their contractile activity, and whether 45Ca2+ movements are inhibited by verapamil or nifedipine. Basal La(3+)-resistant (cellular) 45Ca2+ uptake was significantly greater in the epididymal half (791 +/- 27 nmol g-1) than in the prostatic half (654 +/- 14 nmol g-1) of the rat vas deferens and was unaffected by verapamil (61 microM) or nifedipine (14 microM). Methoxamine (8 microM) was without effect on 45Ca2+ uptake in either half but BaCl2 (1 mM) increased 45Ca2+ uptake by 31% in the prostatic half and by 22% in the epididymal half. The barium-induced increases in 45Ca2+ uptake were markedly reduced or abolished by verapamil (2 microM) or nifedipine (0.3 microM), which at these concentrations have no effect on the rhythmic contractions but abolish the initial small phasic contraction induced by barium. The basal rate of 45Ca2+ efflux from the intact vas deferens (into Ca2+ containing Krebs-Henseleit solution or into Ca-free Krebs-Henseleit solution +/- EGTA 0.05 mM) was not affected by verapamil (61 microM) or nifedipine (14 microM). Methoxamine (8 microM) produced a marked, transient and reversible increase in 45Ca2+ efflux into 2.5 mM CaCl2 Krebs-Henseleit in 50% of the intact vasa deferentia examined which was augmented by verapamil (61 microM). BaCl2 (1 mM) produced a small increase in 45Ca2+ efflux into Ca(2+)-containing and Ca(2+)-free Krebs-Henseleit solutions from some intact vasa deferentia and this was not inhibited by nifedipine (14 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

A liver-specific nitric oxide donor improves the intra-hepatic vascular response to both portal blood flow increase and methoxamine in cirrhotic rats.

BACKGROUND/AIMS: A decreased intra-hepatic nitric oxide (NO) production participates on the pathogenesis of portal hypertension in cirrhosis. We tested the hemodynamic effects of a liver-specific NO donor (NCX-1000) derived from ursodeoxycholic acid in portal hypertensive cirrhotic rats. METHODS: After a 14-day treatment with ursodeoxycholic acid or NCX-1000 by gavage, ascitic cirrhotic rats (CCl4-induced) were used in two studies: (1) in vivo mean arterial pressure (MAP), portal pressure (PP) and superior mesenteric artery (SMA) blood flow measurements before and during progressive blood volume expansion (blood infusion); and (2) in situ liver perfusion to obtain dose/response curves to methoxamine (alpha1-adrenergic agonist) and flow/pressure curves. RESULTS: Basal heart rate, MAP, and PP were similar in both groups. During blood infusion, similar MAP and SMA flow increases were observed in both groups; however, PP increase observed in control rats was blunted in NCX-1000 treated rats (P=0.015). In liver perfusions, flow/pressure curves were similar in both groups; however, NCX-1000-treated livers showed a lower response to methoxamine (P=0.016). cGMP concentration in NCX-1000-treated livers was higher (P=0.015) than in controls. CONCLUSIONS: Treatment with a liver-specific NO donor improves the portal system adaptability to portal blood flow increase and ameliorates the intra-hepatic response to methoxamine in cirrhotic rats.

Animals↗
PubMedDate not supplied

Hemodynamic profiles of methoxamine and B-HT 933 in spinalized ganglion-blocked dogs.

The hemodynamic profiles of methoxamine and B-HT 933 during a stepwise-increased infusion in spinalized ganglion-blocked dogs show that both compounds induce a dose-dependent increase in arterial blood pressure due to an increase in total peripheral resistance. Methoxamine initially also increases cardiac output, which contributes to the increase in blood pressure. The increased cardiac output is the result of an increased stroke volume, because heart rate is unchanged. B-HT 933 increases neither cardiac output nor heart rate. Because neither compound stimulates the heart directly, the increase in stroke volume induced by methoxamine can be due only to an increased venous return. B-HT 933 appears to be devoid of an effect on the capacitance vessels, because stroke volume and cardiac output are unchanged. The present study suggests that under in vivo conditions, postjunctional alpha 2-adrenoceptors in the capacitance vessels of the dog are not functional.

Adrenergic alpha-Agonists↗
PubMed1985

Comparison of the effects of chronic administration of ciclazindol and desipramine on pupillary responses to tyramine, methoxamine and pilocarpine in healthy volunteers.

Twenty-nine healthy volunteers participated in an experiment lasting for 8 weeks: Phase I (2 weeks)--pre-treatment control period; Phase II (4 weeks)--medication with either ciclazindol hydrochloride (50 mg twice daily), or desipramine hydrochloride (50 mg twice daily) or lactose placebo (twice daily) administered in a single-blind fashion; Phase II (2 weeks)--recovery. Experimental sessions took place twice weekly for the photographic assessment of resting pupil diameter, and for the assessment of one of the following pupillary responses: mydriatic response to methoxamine, mydriatic response to tyramine, miotic response to pilocarpine. Resting pupil diameter increased during medication with either ciclazindol or desipramine. Methoxamine-evoked mydriasis and tyramine-evoked mydriasis were antagonized by both ciclazindol and desipramine. Pilocarpine-evoked miosis was potentiated by both ciclazindol and desipramine. The steady-state plasma levels (mean +/- s.e. mean) of the antidepressants were: ciclazindol: 5.90 +/- 0.74 microM; desipramine: 0.60 +/- 0.17 microM. The antagonism of methoxamine-evoked mydriasis is likely to reflect the blockade of postsynaptic alpha 1-adrenoceptors in the iris by the antidepressants, whereas the antagonism of tyramine-evoked mydriasis may reflect both the blockade of uptake of tyramine into presynaptic adrenergic terminals and the blockade of postsynaptic alpha-adrenoceptors. There is no immediate explanation for the potentiation of pilocarpine-evoked miosis by the two antidepressants.

Adolescent↗