Lithium compounds Benzodiazepines

Reduction of the 1//-1,2-benzodiazepines 6 with lithium aluminum hydride results in the dihydro compounds 8, which are dehydrogenated to the 3H-1,2-benzodiazepines 9 by 4-phenyl-4//-l,2,4-triazole-3,5-dione.123 The products readily revert to the 1//-tautomers in the presence of sodium methoxide. 3//-1,2-Benzodiazepines react with 3-chloroperoxybenzoic acid to give mixtures of 1- and 2-oxides, 10 and 11, in which the latter predominate. Treatment of the 2-oxides 11 with nucleophiles provides 3-substituted H- 1.2-benzodiazepines 12. Selected examples are given.124... 

Derivatives of 1-methyl-3//-l,4-benzodiazepine-2,5(l/I,4/I)dione (193) were synthesized by ring closure of substituted 2-(A-chloro-acetyl-A-methylaminoJbenzamides with sodium methoxide in methanol.209 Treatment of 193 with lithium aluminum hydride led to reduction of both carbonyl groups.209 The parent tetrahydro system (194) has been prepared by reaction of the tosylate (195) with 1,2-dibromoethane followed by hydrolysis.210 The preparation of 194 by another route had previously been noted.204 Reaction of 194 with formaldehyde or benzaldehyde gave a compound formulated as 196 (R = H or C6H5).210 Hydrolysis of 196 (R = C6H5) with 0.1 N hydrochloric acid gave 194 while 196 (R = H) was not hydrolyzed at this acidity. 

For treatment-resistant patients who do not respond to SSRIs or TCAs, or to the combination of TCAs/SSRIs with benzodiazepines, other antidepressants have shown at least some beneficial effects in alleviating PD symptoms (e.g. mirtazapine, moclobemide, nefazodone, phenelzine, reboxetine, and venlafaxine). Other agents have also been reported to exert beneficial effects in PD, especially when combined with SSRIs/TCAs (lithium, pindolol, and propranolol). In cases where all treatments have failed, valproate or olanzapine should be considered.2 - ° In order to optimize treatment, patients should avoid or reduce the consumption of compounds that could potentially induce/exacerbate panic attacks (e.g. caffeine, alcohol, and nicotine) and should exercise regularly. i... 

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