Pharmacological Properties of β-Amyrin Palmitate,a Novel Centrally Acting Compound,Isolated from Lobelia inflata Leaves

Abstract— Effects of β-amyrin palmitate isolated from the leaves of Lobelia inflata were studied on the central nervous system of mice and were compared with those of antidepressant drugs, mianserin and imipramine. In the forced swimming test, β-amyrin palmitate, like mianserin and imipramine, reduced the duration of immobility of mice significantly in a dose-dependent manner (5, 10 and 20 mg kg^?1). β-Amyrin palmitate (5, 10 and 20 mg kg^?1) or mianserin (5, 10 and 20 mg kg^?1) elicited a dose-related reduction in locomotor activity of mice and antagonized locomotor stimulation induced by methamphetamine. In contrast, imipramine (5, 10 and 20 mg kg^?1) increased locomotor activity and potentiated methamphet-amine-induced hyperactivity. β-Amyrin palmitate showed no effect on reserpine-induced hypothermia, whilst mianserin (10 mg kg^?1) and imipramine (10 and 20 mg kg^?1) antagonized the reserpine-induced effect. Unlike imipramine, β-amyrin palmitate and mianserin did not affect haloperidol-induced catalepsy, tetrabenazine-induced ptosis and apomorphine-induced stereotypy. β-Amyrin palmitate and imipramine had no effects on the head-twitch response induced by 5-hydroxytryptophan, whereas mianserin (5, 10 and 20 mg kg^?1) decreased it in a dose-dependent manner. A potentiating effect of β-amyrin palmitate (5, 10 and 20 mg kg^?1) on narcosis induced by sodium pentobarbitone was stronger than that of imipramine (10, 20 and 40 mg kg^?1) but weaker than that of mianserin (2·5, 5 and 10 mg kg^?1). These results suggest that β-amyrin palmitate has similar properties in some respects to mianserin and might possess a sedative action. We suggest that β-amyrin palmitate has antidepressant activity with a mianserin-like profile of action.     

An α-adrenoceptor-mediated mechanism of hypoactivity induced by β-amyrin palmitate

Abstract— Inhibitory effects of β-amyrin palmitate in locomotor activity of mice were studied by combining this compound with α-adrenergic agonists or antagonists and a dopaminergic agonist. β-Amyrin palmitate (2·5, 5·0 and 10·0 mg kg^?1, i.p.) decreased locomotor activity of mice in a dose-dependent manner. It enhanced hypoactivity of mice treated with clonidine (0·025 mg kg^?1, i.p.) and antagonized hyperactivity produced by phenylephrine (40 μg, i.c.v.). The inhibitory action of β-amyrin palmitate was not affected by yohimbine (1·5 mg kg^?1, i.p.), but was potentiated by prazosin (0·75 mg kg^?1, i.p.). When combined with a dopaminergic agonist, apomorphine (2·0 mg kg^?1, i.p.), β-amyrin palmitate (5·0 and 10·0 mg kg^?1, i.p.) did not affect locomotor stimulation produced by apomorphine. These results suggest that β-amyrin palmitate might inhibit α₁-adrenoceptors.     

Paclitaxel activity for the treatment of non-Hodgkin's lymphoma: final report of a phase II trial

In order to determine the activity of paclitaxel in patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), we conducted a phase II clinical trial in which eligible patients received paclitaxel 200 mg/m² intravenously over 3 h. Treatment was repeated every 3 weeks. Patients achieving complete or partial responses after two courses of paclitaxel continued to receive therapy for a maximum of eight courses, otherwise they were removed from the study. Of 96 evaluable patients, 45 (47%) had primary refractory disease, and 51 (53%) had relapsed lymphoma. The median number of prior treatment regimens was two (range one to 10 regimens). 45 patients had low-grade, 44 had intermediate-grade, and seven had mantle cell lymphoma. 24/96 patients responded (10 complete and 14 partial remissions) for an overall response rate of 25% (95% CI 17–35%). Patients with relapsed lymphoma had a higher response rate than those with primary refractory disease (19/51=37% v 5/45 =11%; P  < 0.01), and patients with relapsed intermediate-grade lymphoma had a higher response than those with relapsed low-grade lymphoma (9/18=50% v 10/31 = 32%; P  = 0.22). The treatment was very well tolerated with the most common side-effects being alopecia (100%), peripheral neuropathy (35% of ≥ grade II), and arthralgia/myalgia (25% of ≥ grade II). After the first course of paclitaxel, grade III/IV thrombocytopenia and neutropenia were observed in 21% and 23% of the patients respectively. 23 episodes of neutropenic fever developed after 250 courses of paclitaxel therapy (8%). We conclude that paclitaxel, at this dose and schedule, is an active new drug for the treatment of non-Hodgkin's lymphoma. The activity of paclitaxel combination programmes are currently under investigation.     

Racial Disparities in Left Main Stenting: Insights from a Real World Inner City Population

Background

Left main coronary artery (LMCA) disease is associated with significant cardiovascular mortality. The data on patient characteristics' predicting outcomes after LMCA revascularization is sparse.

Methods

A retrospective study of 227 patients with LMCA disease documented on coronary angiography from March 2000 to December 2008. Data included demographic variables, co‐morbidities, cardiac function, and medications. Race was self‐identified. The study outcome was a composite end‐point including myocardial infarction (MI) and all‐cause mortality. Cox proportional hazard analysis was performed to study the effect of various patient attributes including race and gender on the composite end‐point.

Results

Baseline characteristics were specifically compared between individuals who had the study outcome versus those who did not. Mean age was higher in the group with study outcomes when compared to the group without any outcomes (64.3 ± 11.8 years versus 59.2 ± 13.6 years; p = 0.013). After the final multivariate regression analysis, only African American (AA) race and age were found to be independent predictors of adverse cardiac outcome at the end of the first year (race—hazard ratio (HR) 3.82, 95% confidence interval (CI) 1.38–10.62, p = 0.010; age—HR 1.08, 95% CI 1.04–1.13, p < 0.001) and at the end of the study (race—HR 2.71, 95% CI 1.44–5.10, p = 0.002; age—HR 1.03, 95% CI 1.01–1.08, p = 0.017).

Conclusion

In our study of patients with unprotected LMCA disease, AA race, and age were significantly predictive of poor prognosis following revascularization, while gender had no predictive value in prognosticating cardiovascular mortality.