The evaluation of the α-adrenoceptor blocking action of indoramin, phentolamine and thymoxamine on the rat and guinea-pig isolated mesenteric vasculature and aortic spiral preparations

The role of α‐blockade in the treatment of hypertension can be reappraised in the light of a recently developed agent (indoramin) which overcomes the major drawbacks of earlier agents. The medicinal chemistry involved in the discovery and synthesis of indoramin is summarized. Highlights of the animal pharmacology of indoramin are outlined with reference to therapeutic utility as an antihypertensive agent. The mode of action of indoramin can be described as competitive post‐synaptic α‐adrenoceptor antagonism combined with myocardial membrane stabilization. Indoramin is an effective antihypertensive agent in man, without therapeutic problems associated with tachycardia, postural hypotension, tolerance, poor absorption, gastrointestinal disturbances, increased peripheral resistance or increased airways resistance. The pre‐clinical basis for these features has been reviewed.

Section: Animal Pharmacologymentioning

confidence: 99%

Medicinal Chemistry and Animal Pharmacology of Indoramin

Archibald

1981

“…In addition it has been shown to have cardioinhibitory properties, a local anaesthetic action and it blocks histamine and 5-hydroxytryptamine receptors (Alps et al, 1972;Collis & Alps, 1973). The pharmacokinetics of indoramin have been studied in man (Draffan, Lewis, Firmin, Jordan & Dollery, 1976).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of indoramin added to oxprenolol and bendrofluazide as a third agent in severe hypertension.

Marshall¹,

Kettle²,

Barritt³

1980

1 Indoramin, an ot-adrenoceptor blocking agent has been given as a third agent to patients with severe hypertension treated with adequate doses of a ,B-adrenoceptor blocking drug and a thiazide diuretic. 2 A further fall in blood pressure followed the addition of indoramin. With 75 mg twice daily this was on average a fall of 12% of mean arterial pressure in the supine position, 16% standing and 17% after exercise. 3 The rise in blood pressure caused by isometric exercise was not altered by indoramin. 4 Indoramin slowed the heart rate. On 75 mg twice daily the reduction was 14% at rest and 19% after exercise. 5 Side effects of indoramin were sedation, sleep disturbance and vivid dreams.

“…The striking ineffectiveness of indoramin on the tendon jerk may therefore have resulted from its a-adrenoceptor blocking effect being counteracted by uptake1 blockade, while in the vascular system it is as effective an a-blocker as isolated tissue experiments suggest it ought to be (Collis & Alps, 1973;Sugden, 1974).…”

Section: Discussionmentioning

confidence: 99%

“…Isolated tissue experiments have shown consistently that thymoxamine is a weaker ax-adrenoceptor blocker than chlorpromazine or indoramin (Birmingham & Szolcsanyi, 1965;Collis & Alps, 1973;Gorlitz & Frey, 1973;Variava & Turner, 1973;Sugden, 1974).…”

Section: Discussionmentioning

confidence: 99%

Α‐adrenoceptor Blocking Drugs, Pressor Responses to Noradrenaline, and the Ankle Jerk in Man

White

Richens

1974

Changes in pressor responses to infused noradrenaline and in triceps surae jerk amplitude have been measured after the i.v. administration of: chlorpromazine, thioridazine, prochlorperazine, dimethothiazine, indoramin, benzoctamine and clonidine. Each of the drugs blocked pressor responses to noradrenaline and reduced triceps surae jerk amplitude, but little correlation was found between their potencies in the two systems. The effects of the drugs on the triceps surae jerk are not incompatible with an action at a spinal α‐adrenoceptor site, but other pharmacological factors may be involved, such as penetration of the drugs into the central nervous system, and differences in their uptake1 blocking activity.