Neuropharmacological profile of a selective sigma ligand, igmesine: a potential antidepressant.

Igmesine is a selective sigma (sigma(1)) ligand that was reported to exert antidepressant action through an unknown mechanism of action. A number of neurochemical measures were taken in this study in efforts to understand its mode of action. Following 21-day drug treatments, the actions of igmesine on a number of neurochemical measures were investigated. Data obtained showed significant decreases in the densities of beta-adrenergic but not 5-HT(1A), sigma(1) and GABA(B) receptors in fluoxetine (18%), desipramine (DMI, 32%) and igmesine (20%)-treated groups when compared with control. Tyrosine hydroxylase (TH) activity was significantly (30-32%) reduced in all treated groups. Further, fluoxetine and DMI excluding the igmesine-treated groups showed 85 and 40% reductions in serotonin (5-HT) and noradrenaline (NE) neuronal uptake, respectively. Following acute treatment, igmesine lacked activity for monoamine oxidase (MAO) A or B (IC(50)>10 microM). In in vivo studies, at behaviorally active doses, igmesine showed weak effects on the NE uptake but lacked activity in altering 5-HT and DA synthesis or antagonizing selective drug-induced depletion of monoamine neuronal uptake. N-methyl-D-aspartate (NMDA)-induced increases in cGMP was blocked by igmesine indicating that igmesine may interfere with the NMDA receptor/nitric oxide synthase/cGMP pathway. Although it appears that part of the pharmacological actions of igmesine is mediated by the monoaminergic system, there is still need to explore other possible mechanisms of antidepressant action.

Premiums without benefits: waste and inefficiency in the commercial health insurance industry.

The U.S. system of health insurance is wasteful and inefficient. For every dollar the commercial health insurance industry paid in claims in 1988, the industry spent 33.5 cents for administration, marketing, and other overhead expenses. Thus, not including profits, the commercial insurance industry spent 14 times as much on administration, overhead, and marketing per dollar of claims paid as did the Medicare system, and 11 times as much per dollar of claims paid as the Canadian national health system. Had an efficient public program such as Medicare or the Canadian system provided the same amount of benefits, consumers and businesses served by commercial insurers would have saved $13 billion. The sources of waste include excessive marketing costs and administrative costs bloated by discriminatory underwriting practices that segregate the profitable groups and individuals--people who are healthy, young, and in "safe" professions--from everyone else.