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Use of loxapine and amoxapine for the manufacture of a medicament for the treatment of pain

A medicinal salt and prodrug technology, which is applied in the field of application of loxapine and amoxapine in the preparation of drugs for treating pain, can solve the problems that amoxapine cannot control pain, has no pain control effect, etc.

Inactive Publication Date: 2006-01-04
ALEXZA MOLECULAR DELIVERY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The ability, if any, of amoxapine to control pain, especially non-localized pain, cannot be ascertained from this scant amount of information, and there is no information in the prior art as to whether loxapine has any pain-controlling effect of any nature

Method used

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  • Use of loxapine and amoxapine for the manufacture of a medicament for the treatment of pain
  • Use of loxapine and amoxapine for the manufacture of a medicament for the treatment of pain
  • Use of loxapine and amoxapine for the manufacture of a medicament for the treatment of pain

Examples

Experimental program
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Effect test

Embodiment

[0050] The following examples further illustrate the invention described herein and are in no way intended to limit the scope of the invention.

Embodiment 1

[0053]mouse twist test

[0054] Male mice weighing 23-28 g were used for this experiment. Mice were injected with acetic acid (0.5% i.p.). This treatment resulted in recognizable distorted responses in control animals. Starting 5 min after the injection of acetic acid, count the number of twists within 10 min. Ten mice per group were studied. The experiment was conducted double-blind. Evaluation of 5 doses of loxapine and amoxapine (dispersed in 0.2% hypromellose and then dissolved in saline), injected intraperitoneally 30 minutes before administration of acetic acid, compared with the vehicle control group (0.2 % hydroxypropylmethylcellulose in saline solution) for comparison. Dosage levels of loxapine were 0.125, 0.25, 0.5, 1 and 2 mg / kg. Amoxapine dosage levels were 1, 2, 4, 8 and 16 mg / kg. Morphine (8 mg / kg i.p.) administered under the same experimental conditions was used as reference. Data were analyzed using the Mann Whitney U test comparing treated and vehicle ...

Embodiment 2

[0062] Acute and 5-day repeated dose toxicity study of loxapine inhalation aerosol in beagle dogs

[0063] The aim of this study was to investigate the individual maximum tolerated dose and potential toxicity of two clinically relevant doses of loxapine in a 5-day repeated dose study in dogs.

[0064] This study was conducted at CTBR, 87 Senneville Road, Senneville, Quebec, Canada, H9X 3R3, using CTBR's standard operating procedures.

[0065] The test article was loxapine aerosol delivered by oropharyngeal inhalation.

[0066] Animals used at the initiation of treatment were beagles approximately 7-10 months of age, 6-12 kg, purchased from Covance Research Products, Route 2, Box 113, Cumberland, VA 23040. Animals were housed individually in stainless steel cages with strip floors and automatic water valves. Each cage is clearly labeled with a color-coded cage card indicating program, group, animal and tattoo number, and gender. Each animal is uniquely identified by a number...

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Abstract

Loxapine, amoxapine, or salts or prodrugs of either, is effective in alleviating pain, particularly headache pain such as migraine, cluster headaches and tension headaches. Preferably the loxapine or amoxapine is administered systemically, most preferably by inhalation.

Description

Background of the invention [0001] The present invention relates to the treatment and management of pain by administering to a patient in need of such treatment or management an effective amount of loxapine or amoxapine, or a substance providing loxapine or amoxapine in vivo. Further, the present invention relates to the treatment or management of pain by systemically administering (eg by inhalation) loxapine, amoxapine, or substances that provide loxapine or amoxapine in vivo. [0002] Loxapine [2-Chloro-11(4-methyl-1-piperazinyl)diphenyl(b,f)(1,4)oxazepine] is an antipsychotic, used especially in the treatment of psychosis Schizophrenia or related psychosis. It is commercially available in the form of a salt, usually the hydrochloride or succinate. Amoxapine [2-chloro-11(1-piperazinyl)diphenyl(b,f)(1,4)oxazepine] is a known antidepressant that differs from other antidepressants in that It has both antidepressant and antipsychotic properties. Therefore, amoxapine is diffe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/553A61P25/06A61K9/00
CPCA61K9/0073A61K31/553A61K9/007A61P25/04A61P25/06A61P43/00
Inventor R·L·哈利P·蒙扎尔J·D·拉比诺维茨
Owner ALEXZA MOLECULAR DELIVERY
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