Loxapine analogs and methods of use thereof
A technology of compounds and compositions, applied in the directions of drug combinations, active ingredients of heterocyclic compounds, organic chemistry, etc., can solve problems such as difficulty in maintaining insomnia
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Embodiment 1
[0580] Example 1: Synthesis of loxapine analogs
[0581] The compounds of the present invention, and related derivatives, can be synthesized by methods well known to those skilled in the art.
Embodiment 2
[0582] Example 2: Induction of the compounds of the present invention-properties of sleep
[0583] Mammalian sleep can be divided into periods of emergence of sleep, which are periods of rapid eye movement (REM), which is accompanied by adequate brain activity, and non-REM (NREM) sleep periods, which are accompanied by decreased brain activity. . Normally, normal nighttime sleep is basically NREM sleep. Therefore, NREM cumulative time can be used as a standard for measuring the total sleep cumulative time. For example, a significant reduction in NREM sleep can be related to insomnia and form cumulative "sleep debt". For example, the accumulation of physiological needs for sleep will continue until enough extra sleep is obtained. Therefore, the increase in NREM caused by a certain treatment indicates the effectiveness of the treatment in treating insomnia.
[0584] Sleep quality is related to sleep continuity or sleep maintenance. For example, a patient with sleep apnea may wake...
Embodiment 3
[0595] Example 3: Irwin detection for side effects
[0596] Irwin testing can provide information about the potential side effects of the compound on conventional physiological and behavioral functions. The test is carried out by orally administering a 0.25% methylcellulose aqueous solution of the test compound to male Wistar rats. This animal is a species commonly used in this type of research, because background data are easily available.
[0597] The Irwin test detects a variety of factors in the animal to which the test compound is applied. For example, the test can include: cage effects, such as dispersion, breathing rate, mobility, restlessness, combativeness, and bulging eyes; field effects, such as transfer arousal, spatial movement, drooping, startle, tail jumping, Hair erection, contact avoidance, sluggish position, tonic fainting, tight reflexes, visual placing, grip strength, auricle, corneal pain response, and wire manoeuvre; factors found during treatment, such as c...
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