Indoramin and prazosin as adjuncts to beta adrenoceptor blockade in hypertension

Abstract

Two trials were conducted on the effects of adding alpha-adrenoreceptor blockers to the therapy of hypertensive patients already receiving a beta-adrenoreceptor blocking drug with or without a diuretic. The first trial was a single-blind study in which 6 patients receiving long-term combination therapy were crossed from prazosin, 6 to 15 mg/day, to a dose of indo ram in 10 times as large. There was significant bradycardia but little change in blood pressure. The second trial was a double-blind randomized crossover study in which 15 patients completed an 8-wk period of treatment with each of the alpha blockers, administered in random sequence with an intervening 2-wk washout period. Dosage was titrated for optimal antihypertensive effect.The final mean dosages were 76 mg /day for indoramin and 8.2 mg /day for prazosin; the dose ratio was 9.3: I. Both drugs reduced erect systolic blood pressure. Prazosin, but not indoramin, reduccd exercise systolic and diastolic pressures. Indoramin lowered supine and exercise pulse rates. Neither drug affected peak expiratory flow rate or plasma renin activity. Analysis of individual responses in supine diastolic blood pressure showed that there were 9 prazosin and 8 indoramin responders, while 9 of the 21 subjects in the 2 trials failed to respond to either drug. Central side effects were more prominent with indoramin. The combination of one or other of these alpha-adrenoreceptor blockers with preexisting beta-adrenoreceptor blockade improved blood pressure control in 57% of the patients.Indoramin and prazosin are post junctional alpha-adrenoreceptor blocking drugs 4 • 9 which lower blood pressure. 7. 13 Prazosin has been used extensively in the treatment of hypertension and has proved effective alone or in combination with other antihypertensive drugs, particularly beta-adrenoreceptor blockers. '2 Indoramin differs from prazosin in its capability to block histamine and 5-hydroxytryptamine receptors' and has been shown to have cardioinhibitory' and bronchodilator 3 properties. Given alone in sufficient dosage to control the blood pressure of hypertensive patients, indoramin has induced a high incidence of somnolence 5 ; its possible role in combination therapy has not been fully evaluated.

Interaction with Histamine H₁-Receptors and Bronchospasmolytic Effects of Urapidil

“…In vitro studies by previous in vestigators [Schoetensack et al, 1977b] showed that urapidil is a competitive his tamine Hpantagonist sharing this prop erty with other substituted piperazines like cyclizine, chlorcyclizine and mecli zine as prototypes of this class of H|-blockers. A similar action has been found for drugs possessing the chemically related piperidyl group like the ai-adrenoceptor antagonist indoramin which has been shown to exhibit bronchodilating ac tivity in vitro and in vivo [Alps et al, 1972;Bianco et al, 1974;Stokes et al, 1979). This effect is only partly explained by its a-adrenoceptor antagonism but also by prevention of the bronchoconstrictor re sponse to endogenous histamine and se rotonin [Black et al, 1978).…”

Indoramin: 24 Hour Profile of Intra‐arterial Ambulatory Blood Pressure, a Double‐blind Placebocontrolled Crossover Study

“…The use of ganglion blockers, adrenergic neurone blockers and centrally acting agents has declined whilst P-adrenoceptor blocking agents have been used widely. It is now recognized that whereas P-blockade reduces blood pressure, a secondary rise in the peripheral resistance may occur (Frohlich et al, 1968) and the use of an a-blocking agent in combination with P-blockade has been advocated (Beilin & Juel-Jensen, 1972;Stokes et al, 1979). Indoramin is a post-synaptic a-receptor blocking agent which has been shown to possess modest hypotensive activity (Coltart, Meldrum & Royds, 1971;Royds, Coltart & Lockhart,1972;Lewis, George & Dollery, 1973), when assessed by the indirect method of blood pressure recording.…”

Total and Intrarenal Flow Distribution in Healthy Subjects: Technique, Acute Effects of Ibopamine and of Indoramin

“…It was surprising finding that the plasma renin activity became slightly elevated. Previous workers [12,13] did not observe this change in essential hypertensives. The results suggest that indoramin caused afferent arteriolar vasodilation and thereby altered the local renal autoregulatory re sponse so that renin in the juxtamedullary apparatus tended to be discharged into the peripheral circulation [32].…”

“…It acts as a competitive adrenoreceptor blocker on the alpha-1 postsynaptic receptors [9], It lowers blood pressure by causing peripheral vasodilation but without a fall of cardiac out put [10], reflex tachycardia [11] or a rise in plasma renin activity [12,13], In trials performed to date there have been no findings that were suggestive of any adverse renal effects and as a vasodilator it should improve renal blood flow, although a previous study using a smaller intravenous injection of indoramin has showed no effect on effective renal plasma flow [14],…”