Eudesmanolides and diterpenes from Wedelia trilobata and an ent-kaurenic acid derivative from Aspilia parvifolia

The reinvestigation of the aerial parts of Wedelia trilobata afforded, in addition to known compounds, six new eudesmanolides, two ent-kaurenic acid derivatives as well as a degraded one. A corresponding hydroxy compound was present in Gnaphalium undulatum. From Aspilia parvifolia new ent-kaurenic acid epoxides were isolated. The structures were elucidated by spectroscopic methods. The chemotaxonomic situation is discussed briefly.     

Trixikingolides and germacrene derivatives from Trixis species

The investigation of two further Trixis species afforded five new sesquiterpenes related to trixikingolide, six new germacrene derivatives and a sesquiterpene derived from rotundene. Some further known compounds were isolated too, which in part may be of chemotaxonomic significance. The structures were elucidated by spectroscopic methods and a few chemical transformations. The relative position of the ester groups in eight of the new sesquiterpenoids however, could not be established with certainty as partial saponifications were not successful.     

Variance in the production of homovanillic acid and 3-methoxy-4-hydroxyphenethyleneglycol by the awake primate brain

Previous experimental results, using a new technique whereby the production rates of the neurotransmitter metabolites homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) by the awake primate brain are determined, have shown a wide variance in metabolite production among both animal and human subjects. These data suggested that either individual subjects differ in the activity of brain dopamine (DA) or norepinephrine (NE) neurons and/or that the activities of these neurons fluctuate over time. For these reasons a series of experiments were performed in which measures of HVA and MHPG production were obtained at three time points in the same animal (monkeys) over a three hour period. It was found that the group mean values for the production of HVA and MHPG by brain were similar for each of the three time points. However, it was also found that marked variations in HVA and MHPG production occur within a single animal over a three hour period. The coefficients of variation for individual animals for HVA ranged from 9.3 to 31.9% and for MHPG from 10.1 to 62.3%. These variations were not correlated with grossly observable changes in behavioral states. Using an analysis of variance it was found that the variance in MHPG production was significantly greater than that for HVA (F = 6.2, p < 0.05) suggesting that brain NE systems are more liable and/or show greater change than do brain DA systems. These data are interpreted as indicating that in the awake, resting primate brain fluctuations in the activities of DA and NE neurons occur, i.e. there is not a steady, invariant production of metabolites but rather they are produced in pulses of varying lengths. This interpretation of the data is generally consistent with electrophysiological studies which indicate that catecholamine neurons fire in bursts which are then followed by silent periods. Finally, in terms of practical application of the V-A difference technique, these data indicate that replicable group mean estimates of brain HVA and MHPG production can be obtained by averaging values from a single time point whereas accurate information about an individual animal will require multiple samplings.Recent reports from this laboratory have described a method whereby a direct measure of the rates of production of neurotransmitter metabolites such as homovanillic acid (HVA), 3-methoxy-4-hydroxyphenethyleneglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) by the awake primate brain can be determined (1, 2, 3, 4). Since the quantities of HVA, MHPG, and probably 5-HIAA in the brain vary as a function of the activity of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) neurons (1, 5, 6, 7, 8), it is likely that these measures of neurotransmitter metabolite production reflect the functional state of brain DA, NE, and 5-HT neuronal systems. The experimental results thus far obtained with this technique have shown a wide variance in the rates of neurotransmitter metabolite production across both animal and human subjects even though the subjects were not in clearly different behavioral or emotional states (1, 2, 4, 9). These data suggested that either individual subjects differ markedly in the activities of brain DA, NE, and 5-HT neurotransmitter systems and/or that the activity of these systems fluctuates markedly over time. For these reasons, experiments were undertaken in which repeated measures of HVA and MHPG production by brain within the same animal were determined over a three hour period. The results of these experiments, which are reported here, indicate that there are marked changes in brain metabolite production which occur within animals. The implications of these findings for our understanding of the functioning of brain neurotransmitter systems and for the practical applications of this technique are discussed.     

Catecholamine metabolites in human plasma as indices of brain function: Effects of debrisoquin

Metabolites of catecholamine neurotransmitters in plasma are, potentially, an easily available indicator of brain function in man. The peripheral contribution to these metabolites was lowered by debrisoquin sulfate, a monoamine oxidase inhibitor that does not enter the brain. In the monkey, it had been shown that debrisoquin decreased peripheral production of the dopamine metabolite, homovanillic acid (HVA), without changing production by brain; production of the norepinephrine metabolite, 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) was decreased peripherally and in brain. Low-dose debrisoquin administration in man eliminated about 80% of the peripheral contribution to HVA and MHPG in plasma, resulting in a situation in which at least 75% of these metabolites in plasma were from the brain. Under these conditions, HVA and MHPG in plasma had a significant correlation. It could also be estimated that production of MHPG by brain was reduced 55%. Debrisoquin potentially provides a method for studying brain catecholamines through their metabolites in plasma and for treating conditions of brain noradrenergic excess.     

Ein neues germacran-8.12-olid und neue diterpene aus Polymnia canadensis

The aerial parts of P. canadensis afforded a new germacran-8,12-olide and several diterpenic acids. The stereochemistry of the lactone could be established only by careful ¹H NMR investigations of the corresponding pyrazolines formed by addition of diazomethane, while the natural compound and its acetate only show very uncharacteristic NMR spectra. The diterpenes all belong to the rare isokaurene type. The chemotaxonomic aspects are discussed briefly.     

Seven furanoeremophilanes from three Senecio species

The investigation of two further Senecio species and the re-investigation of S. inaequidens afforded, in addition to known compounds, seven new furanoeremophilane derivatives. Six of these are closely related to cacalol, a sesquiterpene type which predominates in the species investigated.