Abstract
Effects of several hydroxylated chlorpromazine metabolites and related compounds on cardiac contractile force were studied using electrically stimulated left atrial preparations of guinea pig hearts. 7,8-Dihydroxychlorpromazine and 7,8-dioxochlorpromazine produced marked positive inotropic effects in μM concentrations. 7,8-Dihydroxyperphenazine and 7-hydroxychlorpromazine had relatively weak inotropic actions. 2-Hydroxydesmethylimipramine also had a weak inotropic action. Other compounds, such as chlorpromazine, 8-hydroxychlorpromazine, 2-hydroxy- or 3-hydroxy-promazine, and 2-hydroxyimipramine, failed to significantly alter cardiac contractile force. The positive inotropic effects of 7,8-dihydroxychlorpromazine or 7,8-dioxochlorpromazine were markedly reduced by pretreatment with (±)-propranolol, indicating the involvement of β-adrenergic mechanisms in the inotropic action of these agents.
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