Prazosin: the first-dose phenomenon.

Graham, Robert M.; Thornell, Ian R.; Gain, J M; Bagnoli, Cristina; Oates, Helen F.; Stokes, Gordon S.

doi:10.1136/bmj.2.6047.1293

Cited by 139 publications

(40 citation statements)

References 3 publications

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“…This property undoubtedly affects the interaction profile in the apomorphine test by favoring decrease of palpebral opening, inhibition of agitation, and suppression of grooming. Tachyphylaxis to the effects of a 1 -adrenoceptor blockade develops rapidly after repeated administration (Graham et al, 1976). For compounds with prominent a 1 -adrenoceptor blocking activity, the present results obtained after single administration in rats may therefore be less predictive for their activity profile after long-term administration in patients.…”

Section: Differentiation Between D 2 Receptor Blockersmentioning

confidence: 55%

Differential Interaction of Neuroleptics with Apomorphine-Induced Behavior in Rats as a Function of Changing Levels of Dopamine Receptor Stimulation

Megens

Hendrickx

Lavreysen

et al. 2013

J Pharmacol Exp Ther

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Twenty-two neuroleptic drugs were studied for interaction with the behavior induced by intravenous injection of apomorphine in rats. All compounds dose-dependently shortened the duration of the apomorphine-induced agitation and-with the exception of clozapine-shortened the onset of the de-arousal grooming that typically occurs immediately after the agitation phase has been terminated. Progressively higher doses were required to antagonize higher levels of apomorphine at earlier time intervals after the intravenous injection. The compounds also decreased palpebral opening, and most of them suppressed grooming behavior at higher doses. Compounds differed considerably in dose increments required for: 1) suppression of grooming, from 0.33 for clozapine to .600 for remoxipride, raclopride, and droperidol; 2) blockade of agitation at 5 minutes after apomorphine, from 2.6 for pimozide to 165 for chlorprothixene and 254 for remoxipride; 3) mild decrease of palpebral opening, from 0.21 for sertindole to 191 for remoxipride; and 4) pronounced decrease of palpebral opening, from 10 for melperone to .820 for raclopride. Only four compounds were able to advance grooming to 15 minutes postapomorphine, but again dose increments varied considerably: droperidol (3.4), pimozide (9.1), raclopride (42), and remoxipride (383). Based on these results obtained in a single animal model, compounds were differentiated in terms of behavioral specificity, incisiveness (the power to counteract the effects of progressively higher apomorphine concentrations), and sedative side-effect liability. Possible explanations for the observed differences and clinical relevance are discussed.

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Section: Differentiation Between D 2 Receptor Blockersmentioning

confidence: 55%

Differential Interaction of Neuroleptics with Apomorphine-Induced Behavior in Rats as a Function of Changing Levels of Dopamine Receptor Stimulation

Megens

Hendrickx

Lavreysen

et al. 2013

J Pharmacol Exp Ther

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“…Although these 'first dose' hypotensive reactions may be asymptomatic, in some patients myocardial ischaemia, transient hemiparesis, dysphasias or coma have developed (Cleland et al, 1985;Hodsman et al, 1983;Packer et al, 1986;Todd & Heel, 1986;Webster, 1987); deaths have also occurred. Similar 'first dose' reactions have been described with phentolamine (Galloway et al, 1975), prazosin (Graham et al, 1976), ketanserin (Waller et al, 1987), labetalol (Maronde, 1983), renin inhibitors (Semple et al, 1988;Zusman et al, 1983), ,-adrenoceptor blockers and adrenergic neurone blockers (Kholeif & Isles, 1989;Webster, 1987). Although the underlying mechanism was originally assumed to be arterial vasodilatation, often enhanced by bradycardia (Cleland et al, 1983;Semple et al, 1988;Webster, 1987), recent evidence suggests that venous dilatation may also be important.…”

mentioning

confidence: 82%

'First dose' hypotension and venodilatation [letter]

Capewell

1991

Brit J Clinical Pharma

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“…A few other clinical investigators have encountered occasional symptomatic hypotension during the course of early clinical studies with bucindolol. 'First dose' hypotension has been a feature of drugs with aadrenoceptor blocking properties such as phentolamine (Galloway et al, 1975) and prazosin (Graham et al, 1976). a-adrenoceptor blockade may also be partly responsible for the high frequency of adverse symptoms when labetalol is added to a diuretic in severe hypertension, particularly at inappropriately high initial doses (McAreavey et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

A comparison of single doses of bucindolol and oxprenolol in hypertensive patients.

Webster¹,

Petrie²,

Robb³

et al. 1985

Brit J Clinical Pharma

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Single doses of bucindolol 50, 100 and 200 mg were compared to placebo and single doses of oxprenolol 40, 80 and 160 mg in seven patients with mild hypertension, in a double‐blind randomized study. Both bucindolol and oxprenolol inhibited exercise induced tachycardia. The mean maximum inhibition of exercise heart rate was similar after each dose of both drugs (20%, P less than 0.001). Bucindolol produced a significantly greater reduction in blood pressure than either oxprenolol or placebo. This was most apparent in standing systolic and diastolic and post‐ exercise systolic blood pressures between 1 and 2 h after dosing and was dose‐related. All seven patients experienced adverse effects related to hypotension within the first 2 h after ingestion of bucindolol 200 mg. Plasma concentrations of oxprenolol, bucindolol or 5‐ hydroxy‐bucindolol, sampled 2 h after dosing, could not be related to either the changes in blood pressure or to the occurrence of symptoms. The results emphasise the need for careful dose‐finding of new drugs prior to their more widespread evaluation in phase 3 studies.

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Prazosin: the first-dose phenomenon.

Cited by 139 publications

References 3 publications

Differential Interaction of Neuroleptics with Apomorphine-Induced Behavior in Rats as a Function of Changing Levels of Dopamine Receptor Stimulation

Differential Interaction of Neuroleptics with Apomorphine-Induced Behavior in Rats as a Function of Changing Levels of Dopamine Receptor Stimulation

'First dose' hypotension and venodilatation [letter]

A comparison of single doses of bucindolol and oxprenolol in hypertensive patients.

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