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BRL 13776: A NOVEL ANTIHYPERTENSIVE AGENT WITH INTERESTING MONOAMINE DEPLETING PROPERTIES
Author(s) -
MELROSE JOANNE,
PALFREYMAN M.G.,
POYSER R.H.,
WHITING R.L.
Publication year - 1977
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1977.tb08428.x
Subject(s) - blood pressure , spontaneously hypertensive rat , medicine , endocrinology , monoamine neurotransmitter , catecholamine , pharmacology , cats , chemistry , serotonin , receptor
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.