Ketanserin analogues: the effect of structural modification on 5-HT2 serotonin receptor binding.

Ketanserin (1) is a fairly selective 5-HT2 antagonist that binds both at 5-HT2A and 5-HT2C receptors. A previous structure-affinity relationship study revealed that the structure of the piperidine-containing ketanserin molecule could be rather severely abbreviated with little effect on 5-HT2A affinity. The present investigation explores several inconsistencies identified in the earlier study and suggests that multiple modes of binding may be possible for ketanserin analogues. Perhaps the nature of the benzylic substituent is the most significant determinant of the manner in which these agents bind at 5-HT2A receptors, and it is possible that certain orientations may avail themselves of an auxiliary binding site. Depending upon the length of the piperidine N-alkyl chain, variation of the benzylic substituent from a carbonyl, to an alcohol, to a methylene group has a nonparallel influence on binding, and this may be further affected by the presence of a second ring nitrogen atom. The results of the present investigation provide evidence that although the structure of ketanserin can be abbreviated, and even modified by conversion of the piperidine ring to a piperazine, the resultant analogues may bind in more than one orientation at the receptors. A key structural feature that may play a prominent role in anchoring or orienting these compounds at 5-HT2A receptors is the benzylic carbonyl group.

Telecommuting. Factors to consider.

1. Telecommuting is a work arrangement in which employees work part time or full time from their homes or smaller telework centers. They communicate with employers via computer. 2. Telecommuting can raise legal issues for companies. Can telecommuting be considered a reasonable accommodation under the Americans With Disabilities Act? When at home, is a worker injured within the course and scope of their employment for purposes of workers' compensation? 3. Occupational and environmental health nurses may need to alter existing programs to meet the distinct needs of telecommuters. Often, there are ergonomic issues and home office safety issues which are not of concern to other employees. Additionally, occupational and environmental health nurses may have to offer programs in new formats (e.g., Internet or Intranet programs) to effectively communicate with teleworkers.