WO1992000103A1 - Pharmaceutical preparations - Google Patents
Pharmaceutical preparations Download PDFInfo
- Publication number
- WO1992000103A1 WO1992000103A1 PCT/GB1991/000992 GB9100992W WO9200103A1 WO 1992000103 A1 WO1992000103 A1 WO 1992000103A1 GB 9100992 W GB9100992 W GB 9100992W WO 9200103 A1 WO9200103 A1 WO 9200103A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- receptor
- uptake inhibitor
- active ingredients
- pharmaceutical product
- product according
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
Definitions
- the present invention relates to pharmaceutical preparations having antidepressant and/or antimigraine activity.
- the present invention provides a pharmaceutical product comprising two or three active ingredients selected from a 5-HT 3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT receptor agonist, as a combined preparation for simultaneous, separate or sequential use in therapy of depression and/or migraine.
- 5-HTo antagonist + 5-HT re-uptake inhibitor
- 5-HT3 antagonist + 5-HT- j _ agonist
- 5-HT3 antagonist + 5-HT re-uptake inhibitor + 5-HT-- agonist.
- 5-HT3 receptor antagonists are as described in WO 89/04660 and WO 90/01996 (Beecham Group p.I.e.), in particular BRL 43694A (granisetron) BRL 46470A (Example 5 in EP-A-247266) ; ondansetron or LY 277359.
- 5-HT receptor antagonists are described in EP-A-410509 (Duphar International Research B.V.), EP-A- 420086 (Fujisawa Pharmaceutical Co., Ltd.), EP-A-403261 (Glaxo Group Limited), EP-A-405784 (Ono Pharmaceutical Co., Ltd.), EP-A-419397 (A/S Ferrosan) , EP-A-417746 (G.O. Searle & Co.) and EP-A-407137 (Yoshitomi Pharmaceutical Industries Ltd.) .
- 5-HT re-uptake inhibitors include the antidepressants, paroxetine and femoxetine (U.S. Patent No. 4007196) , citalopram, sertraline, fluoxetine, clomipramine, fluvoxamine, cianopramine, ifoxetine, cericlamine, SL 810385 (Synthelabo) and seproxetine.
- Suitable examples of 5-HT- ⁇ receptor agonists include those compounds described in GB 2035310A; GB 2124210A; EP-A-145459; GB 2150932; EP-A-147107; GB 2185020A;
- EP-A-303506; EP-A-303507; EP-A-354777; EP-A-254433; and GB 2162522A (Glaxo Group Limited) in particular the compound GR 43175 (su atriptan) or GR 85548; and EP-A-313397 (The Wellcome Foundation Limited) .
- the active components of the product are administered simultaneously although they may be administered separately e.g. the 5-H antagonist administered first.
- the present invention further provides a pharmaceutical composition
- a pharmaceutical composition comprising two or three active ingredients selected from a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT ⁇ receptor agonist in combination with a pharmaceutically acceptable carrier.
- the invention yet further provides the use of two or three active ingredients selected from a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT- ⁇ receptor agonist in the manufacture of a pharmaceutical preparation for simultaneous, separate or sequential use in depression and/or migraine therapy.
- the product of the invention may be administered by the oral route to humans and may be compounded in the form of syrup, tablets or capsule for either separate, sequential or simultaneous administration.
- parenteral administration may be adapted for other modes of administration, for example parenteral administration.
- Other alternative modes of administration include sublingual or transdermal administration.
- compositions containing from about 2.5 to 15 mg of granisetron or 0.01 to 10 mg of BRL 46470A, 10-50 mg of paroxetine and 10-50 mg sumatriptan in a ratio of around 1:4:4 are effective, but this will depend on the activity of the 5-HT receptor antagonist, 5-HT re-uptake inhibitor and/or 5-HT ⁇ agonist.
- a composition of the invention is in the form of a unit-dose.
- unit dose forms include tablets, capsules and powders in sachets or vials.
- Such unit dose forms may contain a total of from 0.01 to 100 mg of a 5-HT3 receptor antagonist and more usually from 0.5 to 50 mg, for example 0.5 to 25 mg such as 0.5, 1, 2, 3, 5, 10, 15 or 20 mg.
- the unit dose form will normally contain from about 5 to 100 mg of the 5-HT re-uptake inhibitor and/or 5 to 100 mg of the 5-HT-L agonist, more usually 10 to 50 mg, for example
- compositions may be administered from 1 to 6 times a day, more usually from 2 to 4 times a day, in a manner such that the daily dose of 5-HT3 receptor antagonist is from 0.5 to 200 mg for a 70 kg human adult and more particularly from 0.5 to 25 mg, and the daily dose of the 5-HT re-uptake inhibitor and/or 5-HT- j ⁇ agonist, is from 10 to 500 mg for a 70 kg human adult and more particularly from 10 to 100 mg.
- compositions of the invention may be formulated with conventional excipients, such as a filler, a disintegrating agent, a binder, a lubricant, a flavouring agent. They are formulated in conventional manner, for example in a manner similar to that used for anti-hypertensive agents.
- the 5-HT3 receptor antagonist, 5-HT re-uptake inhibitor and/or 5-HT- ⁇ receptor agonist are administered in the form of a unit-dose composition, such as a unit dose oral or parenteral composition.
- compositions are prepared by admixture and are suitably adapted for oral or parenteral administration, and as such may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable and infusable solutions or suspensions or suppositories.
- Orally administrable compositions are preferred, in particular shaped oral compositions, since they are more convenient for general use.
- Tablets and capsules for oral administration are usually presented in a unit dose, and contain conventional excipients such as binding agents, fillers, diluents, tabletting agents, lubricants, disintegrants, colourants, flavourings, and wetting agents.
- the tablets may be coated according to well known methods in the art.
- Suitable fillers for use include cellulose, mannitol, lactose and other similar agents.
- Suitable disintegrants include starch, polyvinylpyrrolidone and starch derivatives such as sodium starch glycollate.
- Suitable lubricants include, for example, magnesium stearate.
- Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulphate.
- compositions may be prepared by conventional methods of blending, filling or tabletting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are, of course, conventional in the art.
- Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups, or elixirs, or may be presented as a dry product for reconstitution with water or other suitable vehicle before use.
- Such liquid preparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agents, for example lecithin, sorbitan monooleate, or acacia; non-aqueous vehicles (which may include edible oils) , for example, almond oil, fractionated coconut oil, oily esters such as esters of glycerine, propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl p_-hydroxybenzoate or sorbic acid, and if desired conventional flavouring or colouring agents.
- Oral formulations also include conventional sustained release formulations, such as tablets or granules having an enteric coating.
- fluid unit dose forms are prepared containing a compound of the present invention and a sterile vehicle.
- the compound depending on the vehicle and the concentration, can be either suspended or dissolved.
- Parenteral solutions are normally prepared by dissolving the compound in a vehicle and filter sterilising before filling into a suitable vial or ampoule and sealing.
- adjuvants such as a local anaesthetic, preservatives and buffering agents are also dissolved in the vehicle.
- the composition can be frozen after filling into the vial and the water removed under vacuum.
- Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilised by exposure to ethylene oxide before suspending in the sterile vehicle.
- a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound of the invention.
- compositions will usually be accompanied by written or printed directions for use in the medical treatment concerned.
- each component of the product of the invention may be administered by a different route.
- the present invention yet further provides a method of treating depression and/or migraine in mammals including man, which comprises administering to the suffering mammal an effective amount of a pharmaceutical composition comprising two or three active ingredients selected from a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT-L receptor agonist, in combination with a pharmaceutically acceptable carrier.
- Antidepressant and/or antimigraine activity is assessed in appropriate animal models for determining such activities and in appropriate clinical trial methods.
Abstract
A pharmaceutical product comprising two or three active ingredients as a combined preparation for simultaneous, separate or sequential use in therapy of depression and/or migraine.
Description
PHARMACEUTICAL PREPARATIONS
The present invention relates to pharmaceutical preparations having antidepressant and/or antimigraine activity.
It has now been found that a combination of two or three active agents having different mechanism of action with respect to 5-HT (5-hydroxytryptamine) has good antidepressant and/or antimigraine activity. The effectiveness of the combination is potentially greater than could be predicted from a consideration of the activities of the individual components and it appears that a synergistic effect is being produced.
Accordingly, the present invention provides a pharmaceutical product comprising two or three active ingredients selected from a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT receptor agonist, as a combined preparation for simultaneous, separate or sequential use in therapy of depression and/or migraine.
Suitable combinations are as follows:
5-HTo antagonist + 5-HT re-uptake inhibitor; 5-HT3 antagonist + 5-HT-j_ agonist;
5-HT-j_ agonist + 5-HT re-uptake inhibitor; and
5-HT3 antagonist + 5-HT re-uptake inhibitor + 5-HT-- agonist.
Suitable examples of 5-HT3 receptor antagonists are as described in WO 89/04660 and WO 90/01996 (Beecham Group p.I.e.), in particular BRL 43694A (granisetron) BRL 46470A (Example 5 in EP-A-247266) ; ondansetron or LY 277359.
Other examples of 5-HT receptor antagonists are described in EP-A-410509 (Duphar International Research B.V.), EP-A-
420086 (Fujisawa Pharmaceutical Co., Ltd.), EP-A-403261 (Glaxo Group Limited), EP-A-405784 (Ono Pharmaceutical Co., Ltd.), EP-A-419397 (A/S Ferrosan) , EP-A-417746 (G.O. Searle & Co.) and EP-A-407137 (Yoshitomi Pharmaceutical Industries Ltd.) .
Suitable examples of 5-HT re-uptake inhibitors include the antidepressants, paroxetine and femoxetine (U.S. Patent No. 4007196) , citalopram, sertraline, fluoxetine, clomipramine, fluvoxamine, cianopramine, ifoxetine, cericlamine, SL 810385 (Synthelabo) and seproxetine.
Suitable examples of 5-HT-^ receptor agonists include those compounds described in GB 2035310A; GB 2124210A; EP-A-145459; GB 2150932; EP-A-147107; GB 2185020A;
EP-A-303506; EP-A-303507; EP-A-354777; EP-A-254433; and GB 2162522A (Glaxo Group Limited) in particular the compound GR 43175 (su atriptan) or GR 85548; and EP-A-313397 (The Wellcome Foundation Limited) .
Information with respect to structure and activity of the specific compounds listed hereinbefore may be obtained from well known pharmaceutical industry references, such as "Pharmaprojects", PJB publications Limited, Richmond, Surrey, U.K.
In a preferred aspect, the active components of the product are administered simultaneously although they may be administered separately e.g. the 5-H antagonist administered first.
The present invention further provides a pharmaceutical composition comprising two or three active ingredients selected from a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT^ receptor agonist in combination with a
pharmaceutically acceptable carrier.
The invention yet further provides the use of two or three active ingredients selected from a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT-^ receptor agonist in the manufacture of a pharmaceutical preparation for simultaneous, separate or sequential use in depression and/or migraine therapy.
The product of the invention may be administered by the oral route to humans and may be compounded in the form of syrup, tablets or capsule for either separate, sequential or simultaneous administration.
However, they may be adapted for other modes of administration, for example parenteral administration. Other alternative modes of administration include sublingual or transdermal administration.
Generally, compositions containing from about 2.5 to 15 mg of granisetron or 0.01 to 10 mg of BRL 46470A, 10-50 mg of paroxetine and 10-50 mg sumatriptan in a ratio of around 1:4:4 are effective, but this will depend on the activity of the 5-HT receptor antagonist, 5-HT re-uptake inhibitor and/or 5-HT^ agonist.
In order to obtain consistency of administration it is preferred that a composition of the invention is in the form of a unit-dose. -Suitable unit dose forms include tablets, capsules and powders in sachets or vials. Such unit dose forms may contain a total of from 0.01 to 100 mg of a 5-HT3 receptor antagonist and more usually from 0.5 to 50 mg, for example 0.5 to 25 mg such as 0.5, 1, 2, 3, 5, 10, 15 or 20 mg. The unit dose form will normally contain from about 5 to 100 mg of the 5-HT re-uptake inhibitor and/or 5 to 100 mg of the 5-HT-L agonist, more usually 10 to 50 mg, for example
-4- 10, 15, 20, 25, 30 mg. Such compositions may be administered from 1 to 6 times a day, more usually from 2 to 4 times a day, in a manner such that the daily dose of 5-HT3 receptor antagonist is from 0.5 to 200 mg for a 70 kg human adult and more particularly from 0.5 to 25 mg, and the daily dose of the 5-HT re-uptake inhibitor and/or 5-HT-j^ agonist, is from 10 to 500 mg for a 70 kg human adult and more particularly from 10 to 100 mg.
With the above indicated dosage range, no adverse toxicological effects are indicated with the composition of the invention.
The compositions of the invention may be formulated with conventional excipients, such as a filler, a disintegrating agent, a binder, a lubricant, a flavouring agent. They are formulated in conventional manner, for example in a manner similar to that used for anti-hypertensive agents.
It is greatly preferred that the 5-HT3 receptor antagonist, 5-HT re-uptake inhibitor and/or 5-HT-^ receptor agonist, are administered in the form of a unit-dose composition, such as a unit dose oral or parenteral composition.
Such compositions are prepared by admixture and are suitably adapted for oral or parenteral administration, and as such may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable and infusable solutions or suspensions or suppositories. Orally administrable compositions are preferred, in particular shaped oral compositions, since they are more convenient for general use.
Tablets and capsules for oral administration are usually presented in a unit dose, and contain conventional
excipients such as binding agents, fillers, diluents, tabletting agents, lubricants, disintegrants, colourants, flavourings, and wetting agents. The tablets may be coated according to well known methods in the art.
Suitable fillers for use include cellulose, mannitol, lactose and other similar agents. Suitable disintegrants include starch, polyvinylpyrrolidone and starch derivatives such as sodium starch glycollate. Suitable lubricants include, for example, magnesium stearate. Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulphate.
These solid oral compositions may be prepared by conventional methods of blending, filling or tabletting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are, of course, conventional in the art.
Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups, or elixirs, or may be presented as a dry product for reconstitution with water or other suitable vehicle before use. Such liquid preparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agents, for example lecithin, sorbitan monooleate, or acacia; non-aqueous vehicles (which may include edible oils) , for example, almond oil, fractionated coconut oil, oily esters such as esters of glycerine, propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl p_-hydroxybenzoate or sorbic acid, and if desired conventional flavouring or colouring agents.
Oral formulations also include conventional sustained release formulations, such as tablets or granules having an enteric coating.
For parenteral administration, fluid unit dose forms are prepared containing a compound of the present invention and a sterile vehicle. The compound, depending on the vehicle and the concentration, can be either suspended or dissolved. Parenteral solutions are normally prepared by dissolving the compound in a vehicle and filter sterilising before filling into a suitable vial or ampoule and sealing. Advantageously, adjuvants such as a local anaesthetic, preservatives and buffering agents are also dissolved in the vehicle. To enhance the stability, the composition can be frozen after filling into the vial and the water removed under vacuum.
Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilised by exposure to ethylene oxide before suspending in the sterile vehicle. Advantageously, a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound of the invention.
As is common practice, the compositions will usually be accompanied by written or printed directions for use in the medical treatment concerned.
It will be appreciated that each component of the product of the invention may be administered by a different route.
The present invention yet further provides a method of treating depression and/or migraine in mammals including man, which comprises administering to the suffering mammal an effective amount of a pharmaceutical composition
comprising two or three active ingredients selected from a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT-L receptor agonist, in combination with a pharmaceutically acceptable carrier.
Standard methods for assessing 5-HT3 receptor antagonist activity, 5-HT-^ receptor agonist activity and 5-HT re-uptake inhibition activity are known in the art, and are, for example, described or referenced in the aforementioned patent publication references.
Antidepressant and/or antimigraine activity is assessed in appropriate animal models for determining such activities and in appropriate clinical trial methods.
Claims
1. A pharmaceutical product comprising two or three active ingredients selected from a 5-HT3 receptor 5 antagonist, a 5-HT re-uptake inhibitor and a 5-H -L receptor agonist, as a combined preparation for simultaneous, separate or sequential use in therapy of depression and/or migraine.
102. A pharmaceutical product according to claim 1 comprising two active ingredients which are a 5-HT3 receptor antagonist and a 5-HT re-uptake inhibitor.
3. A pharmaceutical product according to claim 1
15 comprising two active ingredients which are a 5-HT3 receptor antagonist and a 5-HT-^ receptor agonist.
. A pharmaceutical product according to claim 1 comprising two active ingredients which are a 5-HT-^ receptor
20 agonist and a 5-HT re-uptake inhibitor.
5. A pharmaceutical product according to claim 1 comprising three active ingredients which are a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT--
25 receptor agonist.
6. A pharmaceutical product according to claim 1 wherein a 5-HT3 receptor antagonist is selected from those described in WO 89/04660 and WO 90/01996. 30
7. A pharmaceutical product according to claim 1 wherein a 5-HT re-uptake inhibitor is selected from paroxetine, femoxetine, citalopram, sertraline, fluoxetine, clomipramine, fluvoxamine, cianopramine, ifoxetine,
35 cericlamine, SL 810385 and seproxetine.
8. A pharmaceutical product according to claim 1 wherein the 5-HT^ receptor agonist is sumatriptan.
9. A pharmaceutical composition comprising two or three 5 active ingredients selected from a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT-^ receptor agonist in combination with a pharmaceutically acceptable carrier.
10 10. The use of two or three active ingredients selected from a 5-HT3 receptor antagonist, a 5-HT re-uptake inhibitor and a 5-HT-|_ receptor agonist in the manufacture of a pharmaceutical preparation for simultaneous, separate or sequential use in depression and/or migraine therapy.
15
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB909014365A GB9014365D0 (en) | 1990-06-28 | 1990-06-28 | Pharmaceutical preparations |
| GB909014364A GB9014364D0 (en) | 1990-06-28 | 1990-06-28 | Pharmaceutical preparations |
| GB909014367A GB9014367D0 (en) | 1990-06-28 | 1990-06-28 | Pharmaceutical preparations |
| GB9014364.5 | 1990-06-28 | ||
| GB909014354A GB9014354D0 (en) | 1990-06-28 | 1990-06-28 | Pharmaceutical preparations |
| GB9014354.6 | 1990-06-28 | ||
| GB9014367.8 | 1990-06-28 | ||
| GB9014365.2 | 1990-06-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1992000103A1 true WO1992000103A1 (en) | 1992-01-09 |
Family
ID=27450525
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB1991/000992 WO1992000103A1 (en) | 1990-06-28 | 1991-06-20 | Pharmaceutical preparations |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU8072691A (en) |
| IE (1) | IE912237A1 (en) |
| WO (1) | WO1992000103A1 (en) |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994026270A1 (en) * | 1993-05-06 | 1994-11-24 | Lts Lohmann Therapie-Systeme Gmbh & Co. Kg | Transdermal therapeutic systems for the administration of serotonin agonists |
| EP0747049A1 (en) * | 1995-06-08 | 1996-12-11 | Eli Lilly And Company | Use of tachykinin antagonists in combination with serotonin agonists or serotonin reuptake inhibitors for the manufacture of a medicament for the treatment of allergic rhinitis |
| US5589511A (en) * | 1990-08-13 | 1996-12-31 | Sepracor Inc. | Method for treating migraine headaches using optically pure S(+) fluoxetine |
| WO1997029739A2 (en) * | 1996-02-15 | 1997-08-21 | Janssen Pharmaceutica N.V. | Use of 5ht4 receptor antagonists for overcoming gastrointestinal effects of serotonin reuptake inhibitors |
| EP0958824A3 (en) * | 1998-05-22 | 1999-12-01 | Eli Lilly And Company | Olanzapine (zyprexa) in combination with fluoxetine (prozac), lithium or anticonvulsant for therapy of refractory depression |
| WO1999061014A2 (en) * | 1998-05-28 | 1999-12-02 | Sepracor Inc. | Compositions and methods employing r(-) fluoxetine and other active ingredients |
| EP0966967A3 (en) * | 1998-05-29 | 2000-05-31 | Eli Lilly And Company | Combination therapy of olanzapine (zyprexa) and fluoxetine (prozac) for treatment of bipolar disorder |
| EP1077704A1 (en) * | 1998-05-21 | 2001-02-28 | Eli Lilly And Company | Combination therapy for treatment of depression |
| EP1230921A1 (en) * | 2001-02-02 | 2002-08-14 | Pfizer Products Inc. | Combination treatment for depression |
| US6517866B1 (en) | 1997-07-01 | 2003-02-11 | Pfizer Inc. | Sertraline salts and sustained-release dosage forms of sertraline |
| WO2005023767A2 (en) | 2003-09-10 | 2005-03-17 | Brentwood Equities Ltd. | Diastereomers of 4-aryloxy-3-hydroxypiperidines |
| US6960577B2 (en) | 1998-05-22 | 2005-11-01 | Eli Lilly And Company | Combination therapy for treatment of refractory depression |
| US7034059B2 (en) | 2001-07-02 | 2006-04-25 | Sepracor Inc. | Methods of using norfluoxetine |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1989004660A1 (en) * | 1987-11-14 | 1989-06-01 | Beecham Group Plc | 5-ht3 receptor antagonists for treatment of cough and bronchoconstriction |
-
1991
- 1991-06-20 AU AU80726/91A patent/AU8072691A/en not_active Abandoned
- 1991-06-20 WO PCT/GB1991/000992 patent/WO1992000103A1/en unknown
- 1991-06-26 IE IE223791A patent/IE912237A1/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1989004660A1 (en) * | 1987-11-14 | 1989-06-01 | Beecham Group Plc | 5-ht3 receptor antagonists for treatment of cough and bronchoconstriction |
Non-Patent Citations (2)
| Title |
|---|
| Chemical Abstracts, vol. 107, no. 23, 7 December 1987, (Columbus, Ohio, US), D.R. Thomas et al.: "Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor", see pages 43,44, abstract 211787c, & Psychopharmacology (Berlin) 1987, 93(2), 193-200 * |
| Chemical Abstracts, vol. 113, no. 7, 13 August 1990, (Columbus, Ohio, US), A.J. Sleight et al.: "In vivo effects of sumatriptan (GR 43175) on extracellular levels of 5-HT in the guinea pig", see page 52, abstract 52433q, & Neuropharmacology 1990, 29(6), 511-13 * |
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5589511A (en) * | 1990-08-13 | 1996-12-31 | Sepracor Inc. | Method for treating migraine headaches using optically pure S(+) fluoxetine |
| WO1994026270A1 (en) * | 1993-05-06 | 1994-11-24 | Lts Lohmann Therapie-Systeme Gmbh & Co. Kg | Transdermal therapeutic systems for the administration of serotonin agonists |
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Also Published As
| Publication number | Publication date |
|---|---|
| IE912237A1 (en) | 1992-01-01 |
| AU8072691A (en) | 1992-01-23 |
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