BRL 13776: a novel antihypertensive agent with interesting monoamine depleting properties.

Abstract

1. Oral doses of 10-100 mg/kg of BRL 13776 lowered the blood pressure of both deoxycorticosterone acetate (DOCA)/NaCl-treated hypertensive rats and untreated normotensive rats. 2. BRL 13776 (100 mg/kg, orally) also reduced the blood pressure of renal hypertensive cats (cellophane perinephritis model). 3. No tolerance developed to the blood-pressure lowering action of BRL 13776 when an oral daily dose of 100 mg/kg was administered repeatedly for up to 15 days to hypertensive rats and cats. 4. The fall in blood pressure to BRL 13776 in rats was associated with a reduction of tissue catecholamines. 5. The catecholamine depletion occurred in all the peripheral tissues examined but in the brain was restricted to certain regions, these being the hind-brain on single dosing and the hind-brain, hypothalamus and mid-brain on repeated dosing. Catecholamine levels in the cerebral hemispheres were not affected by either single or repeated doses of BRL 13776. 6. BRL 13776 caused some reduction of the 5-hydroxytryptamine content of the heart but not of whole brain or any brain region. 7. Neither single doses (up to 900 mg/kg orally) nor repeated doses (100-300 mg/kg orally) of BRL 13776 produced any significant behavioural effects in animals. 8. BRL 13776 is a new type of agent to display both antihypertensive and monoamine-depleting properties. The reduction of noradrenaline in certain brain regions may be a cause of the antihypertensive response but depletion in the periphery could contribute in a major or minor way. The differential action on noradrenaline in the brain together with the lack of effect on 5-hydroxytryptamine might also explain the apparent absence of behavioural effects.

• Authors: J Melrose, M G Palfreyman, R H Poyser, R L Whiting
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 61 Issue 3 Pg. 357-69 (Nov 1977) ISSN: 0007-1188 [Print] England
• PMID: 588803 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Benzopyrans
• Biogenic Amines
• Chromans
• Pyridines
• Desoxycorticosterone
• BRL 13776

Topics

• Animals
• Antihypertensive Agents (pharmacology)
• Behavior, Animal (drug effects)
• Benzopyrans (pharmacology)
• Biogenic Amines (metabolism)
• Brain Chemistry (drug effects)
• Cats
• Chromans (pharmacology)
• Desoxycorticosterone (pharmacology)
• Hypertension (physiopathology)
• Male
• Pyridines (pharmacology)
• Rats