Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing
|Title:||Method of inhibiting neurotransmitter activity using microencapsulated 3-piperidiny2-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles|
|Abstract:||A pharmaceutical composition comprising a biodegradable and biocompatible composition comprising a 1,2 benzazole within a polymeric matrix. The 1,2 benzazole composition, pharmaceutically acceptable acid addition salts thereof, are potent antagonists of a series of neurotransmitters, particularly serotonin and dopamine. A method of inhibiting both serotonergic overactivity and dopaminergic overstimulation in animals is provided by administration of a biodegradable and biocompatible microparticle composition comprising a 1,2 benzazole or a pharmaceutically acceptable acid addition salt thereof. A method of treating warm blooded animals suffering from psychotic disorders, and a method of preparing the biodegradable and biocompatible composition are also described.|
|Inventor(s):||Mesens; Jean (Wechelderzande, BE), Rickey; Michael E. (Loveland, OH), Atkins; Thomas J. (Cincinnati, OH)|
|Assignee:||Janssen Pharmaceutica (BE) Alkermes Controlled Therapeutics Inc. II (MA)|
1. A method of inhibiting serotonergic activity or dopaminergic activity in animals wherein said method comprises administering a microparticle composition comprising a
1,2-benzazole of the formula ##STR15## or a pharmaceutically acceptable acid addition salt thereof, wherein R is hydrogen or alkyl of 1 to 6 carbon atoms;
R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen, halo, hydroxy, alkyloxy of 1 to 6 carbon atoms, and C alkyl of 1 to 6 carbon atoms;
X is O or S;
Alk is C.sub.1-4 alkanediyl; and
Q is a radical of formula ##STR16## wherein R.sup.3 is hydrogen or alkyl of 1 to 6 carbon atoms;
Z is --S--, --CH.sub.2 --, or --CR.sup.4 .dbd.CR.sup.5 --; where R.sup.4 and R.sup.5 are independently selected from the group consisting of hydrogen or alkyl of 1 to 6 carbon atoms;
A is a bivalent radical --CH.sub.2 --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --CH.sub.2 -- or CR.sup.6 .dbd.CR.sup.7 --; where R.sup.6 and R.sup.7 are independently selected from the group consisting of hydrogen, halo, amino or alkyl of 1 to 6 carbon atoms; and
R.sup.8 is hydrogen or hydroxyl;
and a biodegradable and biocompatibly acceptable microparticle polymer carrier.
2. The method of claim 1, wherein the microparticle polymer carrier polymeric matrix is selected from the group consisting of poly(glycolic acid), poly-D,L-lactic add, poly-L-lactic acid, copolymers of the foregoing, poly(aliphatic carboxylic acids), copolyoxalates, polycaprolactone, polydioxonone, poly(ortho carbonates), poly(acetals), poly(lactic acid-caprolactone), polyorthoesters, poly(glycolic acid-caprolactone), polyanhydrides; albumin, casein, and waxes.
3. The method of claim 1, wherein said 1,2-benzazole comprises about 35 to 40 wt. % of said microparticles.
4. The method of claim 1, wherein said microparticles range in size from 25 to 180 microns.
5. The method of claim 1, wherein the 1,2-benzazole is selected from the group consisting of 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1piperidinyl]ethyl]-6,7,8,9-tetra hydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one or a pharmaceutically acceptable acid addition salt thereof.
Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.