The synthesis of 1-methyl-promazine, 4-hydroxymethyl-iminodibenzyl, and 4-bromo-5-trimethylsilyl-iminodibenzyl via dilithiation and ¹H-NMR's are described. Molecular modeling was done for the latter compound. The heat of dissociation was 30.6 kcal/mole for the lowest energy conformer. Rotational energies were examined for three bonds. The IC₅₀ values for inhibition of neurotransmitter uptake by rat brain synaptosomes were determined for a series of 1-substituted promazines, and 4-substituted imipramines. 1-Substituted promazines were fair inhibitors of serotonin uptake with an average IC₅₀ of 2000 nm. Their potency for inhibiting norepinephrine uptake was difficult to assess due to poor assay reproducibility, and the average IC₅₀ was estimated at 200 to 1700 nm. Serotonin, but not norepinephrine, uptake inhibition was increased with additional ring substitution at C(2) with a trifluoromethyl group. The 4-substituted imipramines were equal or slightly decreased in potency to unsubstituted imipramine for uptake inhibition of both neurotransmitters. IC₅₀'s were also reported for imipramine and desipramine.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/291828 |
| Date | January 1988 |
| Creators | Peters, Jennifer Margaret, 1956- |
| Contributors | Martin, Arnold R. |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | en_US |
| Detected Language | English |
| Type | text, Thesis-Reproduction (electronic) |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
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