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Although cocaine has a fascinating and complex medicinal history in man, its natural function in plants is unknown. The present studies demonstrate that cocaine exerts insecticidal effects at concentrations which occur naturally in coca leaves. Unlike its known action on dopamine reuptake in mammals, cocaine's pesticidal effects are shown to result from a(More)
Alzheimer's disease, in its early onset familial form, is known to be a heterogeneous disorder. This suggests that the different degenerative mechanisms, initiated by different genetic causes and ending in the shared phenotype of the disease, should intersect at some point in the degenerative cascade to form a 'bottleneck' from which the pathological(More)
BACKGROUND AND PURPOSE The causes of volume depletion and hyponatremia after subarachnoid hemorrhage are not fully understood but may be in part due to natriuresis or "cerebral salt wasting." Because previous studies using infrequent hormone sampling have given inconsistent results, we determined if elevations in atrial natriuretic factor concentrations(More)
The effect of carbamazepine treatment on CSF-somatostatin-like immunoreactivity (SLI) in patients suffering from temporal lobe epilepsy was investigated. A baseline lumbar puncture was performed on 12 patients and 10 normal volunteers. A second tap was repeated only in patients when they were on peak of carbamazepine concentration for 10 days. Levels of(More)
Over the past decade, high throughput screening (HTS) has become the focal point for discovery programs within the pharmaceutical industry. The role of this discipline has been and remains the rapid and efficient identification of lead chemical matter within chemical libraries for therapeutics development. Recent advances in molecular and computational(More)
Prosecution of positive allosteric modulator (PAM) targets demands a specialized assay toolset. Many GPCR or ion channel targets are adaptable to functional assays whereby PAM efficacy can be inferred from left or rightward shifts in the concentration-response curves of orthosteric agonist. The inherent emphasis on throughput and occasional paucity of(More)
Octopamine, a putative phenylethylamine neurotransmitter present in the firefly, has been found to be a potent stimulator of cyclic AMP synthesis in the larval light organ. In the same tissue, octopamine causes a small inhibition of phosphodiesterase activity. Because of the relatively simple anatomical relationships present in the larval light organ,(More)
We describe a novel compound, (-)-N-(2-ethoxyphenyl)-N'-(1,2,3-trimethylpropyl)-2-nitroethene-1, 1-diamine), Bay x9227, that demonstrates dose-dependent hyperpolarizing activity of remarkable potency (EC50 3 picomolar) and selectivity for CNS neurons and clonal neurotypic cells compared to smooth muscle cells. Single cell membrane potential measurements(More)
Recent studies indicate that selective beta 2-adrenoceptor antagonists may be of use in the treatment of glaucoma. ICI 118,551, its desmethyl-, didesmethyl-, and ethyl- analogues, and a putative highly beta 2-selective binary aryloxypropanolamine (4d) have been evaluated for their ability to inhibit beta-adrenergic-stimulated adenylate cyclase activity in(More)