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Buspirone is an anxiolytic drug which exerts several central effects. It antagonizes presynaptic inhibitory DA2 autoreceptors at dopaminergic neurons and acts as an agonist for 5-HT1A inhibitor autoreceptors at serotonergic cells. Thus, buspirone respectively enhances and depresses the firing rates of both type of neurons. At doses which correlate with dopaminergic stimulation, but not 5-HT inhibition, buspirone also increases the firing rates of the central noradrenergic cells. We measured levels of circulating neurotransmitters before and up to 240 minutes after the oral administration of 20 mg of buspirone in 32 healthy volunteers. Buspirone significantly increased levels of noradrenaline, dopamine, and free serotonin but did not affect levels of adrenaline, tryptophane, or platelet serotonin. Small but significant drops in systolic blood pressure and heart rate were observed after buspirone ingestion. Atropine administration before buspirone ingestion annulled the free serotonin increase as well as systolic blood pressure-heart rate decrease. We found significant positive correlations between noradrenaline and dopamine levels. The strength and significance of these correlations were increased by using the noradrenaline/adrenaline ratio instead of noradrenaline absolute values. This finding indicates that increases in both noradrenaline and dopamine arise from sympathetic nerves rather than the adrenal glands. We also found significant negative correlations between free serotonin increases and systolic blood pressure-heart rate decreases. Our results indicate that buspirone stimulates central sympathetic activity. These acute effects of buspirone are reflected in an increased peripheral neural sympathetic activity, but not adrenal sympathetic activity in healthy individuals. In addition, buspirone increases free serotonin plasma concentrations and decreases systolic blood pressure plus heart rate levels through mechanisms associated with parasympathetic activation.

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The effects of single and combined selective blockade of the sympathetic alpha-and beta-receptors were examined in patients with severe hypertension (diastolic pressure > I20 mmHg) uncomplicated by cardiac or renal failure. Given In uncomplicated essential hypertension the raised blood pressure is accompanied by a normal cardiac output (Taylor, Donald, and Bishop, I957). The increased peripheral resistance is uniformly distributed throughout all the regional circulations and resides predominantly in the peripheral arterioles (Freis, I960). These vessels regulate the resistance in many of the regional vascular beds, and particularly in the kidney, through sympathetic alphaadrenergic receptors (Moran, I966).Thus it is reasonable to expect that drugs which possess both vasodilator properties and also the ability to inhibit stimulation of the adrenergic alpha-receptors may offer substantial advantages over other less specific agents in the treatment of hypertensive vascular disease. Phentolanine, an alpha-receptor antagonist with conspicuous vasodilator properties (Taylor et al., i965a, b; Majid, Sharma, and Taylor, 197i), has been shown to be effective in acutely lowering the blood pressure of hypertensive patients (Taylor et al., i965a I965a; Majid et al., 197I). For this reason it is logical to combine drugs that block both the alphaand beta-adrenoreceptors so that the reflex increase in sympathetic stimulation of the heart that occurs in response to the fall in blood pressure induced by alpha-receptor blockade is prevented by inhibition of the cardiac beta-receptors.The following investigation was, therefore, undertaken to test this thesis by acute haemodynamic studies in patients with severe hypertensive disease and to determine the clinical effectiveness of the combination of oral alpha-and beta-receptor antagonists in the longer term treatment of these patients.Patients and methodsTwelve patients with severe uncomplicated essential hypertension were studied. Five were men, average age 47 years (range 44 to 50 years) and average weight 89 kg (range 84 to 98 kg); 7 were women average age 41 years (range 34 tO 49 years) and average weight 60 kg (range 49 to 83 kg). Seven patients presented with severe headaches which had proved intractable to other antihypertensive drugs, singly or in combination. In the remainder a high blood pressure was discovered during routine medical examination for minor illnesses. The lowest diastolic pressure measured in the supine position by doctors in the ward persistently exceeded I20 mmHg (range I20 to I50) in all patients during their hospital on 12 May 2018 by guest. Protected by copyright.

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