NEW PHARMACEUTICAL PREPARATION AND METHOD

Abstract: A new pharmaceutical preparation comprising at least one amine, or an analogue, a precursor or a pharmaceutically acceptable salt thereof capable of being taken up by and stored in mast cells and released therefrom upon binding of an allergen to a receptor on the mast cells. This pharmaceutical preparation is intended for treatment and/or prevention of allergy. A method for treatment and/or prevention of allergy, comprising administration to a patient of an effective amount of at least one amine, or an analogue, a precursor or a pharmaceutically acceptable salt thereof that is taken up by and stored in the patient's mast cells, and released therefrom upon binding of an allergen to a receptor on the mast cells. The above mentioned substance must not be histamine or a substance with histaminergic effects. It is preferably a biogenic monoamine, or an analogue, a precursor or a pharmaceutically acceptable salt thereof, and most preferably 5-HTP or a derivative thereof.

Description: NEW PHARMACEUTICAL PREPARATION AND METHOD Technical field of the invention The present invention relates to a new pharmaceutical preparation and a new method for treatment and/or prevention of allergy. Background art Allergic conditions, such as allergic rhinitis (hay fever) , allergic conjunctivitis and certain forms of urticaria and bronchial asthma, are the results of altered immune responses to environmental antigens derived form many sources, such as pollen, or components of dust or food. These are normally weak antigens to which most people do not show any adverse reactions. However, when certain susceptible persons are exposed to such antigens, the production of immunoglobulin E (IgE) antibodies by specific B-lymphocytes is initiated. These antibodies attach themselves to receptors (IgE-receptors) on the surfaces of mast cells, a cell type found in connective tissue and in mucous membranes . Subsequent exposure to the antigen (allergen) results in its binding to these receptor-antibody complexes. The binding triggers the release of an array of very active molecules from the mast cells. When released into the tissues these molecules initiate the allergic response by their action on blood vessels, mucous glands and smooth muscle. They are therefore often referred to as mediators of allergy. Thus, mast cells play a key roll in allergic reactions. They provide mediators triggering the classical allergic symptoms such as itching, erythema (redness) , oedema (swelling) , mucous secretion and bronchial muscular spasm. The mediators are either pre-formed and stored in the mast cells, or newly formed in rapid response to allergen binding. A prominent example of a mediator which is pre- formed and stored in the cells is histamine. Many of the symptoms and signs typically associated with allergic rhinitis, allergic conjunctivitis as well as with certain types of urticaria and bronchial astma, have been ascribed to the action of histamine released from the mast cells. One important approach in the treatment of allergic disorders is therefore to reduce or counteract the action of histamine. This can be done in several fundamentally different ways: 1) Blocking the effect of released histamine: This has, until now, been the most successful pharmacological strategy, and has resulted in the development of a series of antihistamines, which are molecules blocking the effects of histamine by competing with its binding to its receptors on effector cells. The most recently developed antihistamines (the so called second generation of antihistamines) bind more ore less specifically to the Hi-receptors, which mediate the early-phase allergic responses referred to above. Antihistamines have undesired side effects, the most serious of which being drowsiness and fatigue. These side effects have been reduced or, in some cases, practically been eliminated in the second generation of HI -blocking drugs, but other side effects remain or have been added. Thus, since the 1990s there has been reports in the literature on rare but potentially serious cardiac arrythmias associated with the use of some of these drugs (see Hey et al., Arzneimittel-Forschung. 46(2):153-8, 1996). Obviously drugs so widely used as oral antihistaminics should have a very low risk profile. 2) Blocking the production of histamine in the mast cells: In order to avoid undesirable effects, this strategy would require the blocking of histamine synthesis specifically in the mast cells. This has not yet been achieved. Histamine has biological functions in other systems that must not be affected. Thus it functions as neurotransmitter in the central nervous system and par- ticipates in the regulation of acid secretion in the stomach. A general blocking of histamine synthesis by the use of histamine synthesis inhibitors is therefore not feasible in the treatment of allergy. 3) Blocking of the secretion process: The secretion process is the mechanism by which mediators are released from the mast cell. The blocking of this process would require the identification and subsequent inhibition of a link in the secretory signal transduction chain, a link specific or unique for the mast cell secretion and not shared with other secretory or signalling cell systems. This has not yet been accomplished. Sodium chro- moglycate and its more recently developed analogue Nedocromil sodium inhibit both immunologic and non- immunologic mast cell secretion via an unknown mechanism, which has been simply referred to as "mast cell stabilisation" . A similar, not yet understood, but apparently less pronounced anti-secretory action has been reported for some of the members of the second genera- tion of histamine Hi-blocking drugs (e.g. ceterizine and loratidine) . 4) Blocking of the IgE receptor and its function: This has been attempted by the use of specifically designed hybrid antibody molecules capable of binding to IgE re- ceptors, blocking IgE binding, but incapable of initiation IgE synthesis by B-cells or secretion by mast cells. Clinical tests of such molecules have not yet been published. Summary of the invention The object of the present invention is to provide a new pharmaceutical preparation and a new method for treatment and/or prevention of allergy, said pharmaceutical preparation and method being based on a different concept than the ones used today, namely the fact that mast cells can store other types of amines besides histamine; said pharmaceutical and method will not have the disadvantages and drawbacks connected with known pharmaceuticals and methods. Unlike most other pharmaceuticals this new drug will be designed to be released locally at the site of the in- jurious tissue reaction from mast cells where its concentration has been built up by the administration of comparatively low doses of the drug or its precursor. By this release effective, comparatively high local extracellular concentrations can be attained which are con- trolled by the degree of allergic mast cell (and tissue) response. The systemic concentration of the drug does not have to be increased, unlike when traditional systemic treatment with antiallergic drugs is used. Low systemic concentrations will reduce the risk of undesirable, po- tentially harmful side effects from irrelevant organ systems distant to the site of allergic tissue reaction. Thus, the present invention relates to a pharmaceutical preparation comprising at least one amine or an analogue, a precursor or a pharmaceutically acceptable salt thereof capable of being taken up by and stored in a patient's mast cells and released therefrom upon binding of an allergen to a receptor on the mast cells. Furthermore, the invention relates to the use of at least one amine or an analogue, a precursor or a pharma- ceutically acceptable salt thereof capable of being taken up by and stored in mast cells and released therefrom upon binding of an allergen to a receptor on the mast cells for the production of a pharmaceutical preparation for treatment and/or prevention of allergy. Finally, the invention relates to a method for treatment and/or prevention of allergy, comprising administration to a patient of an effective amount of at least one amine or an analogue, a precursor or a pharmaceutically acceptable salt thereof, that is taken up by and stored in a patient's mast cells, and released therefrom upon binding of an allergen to a receptor on the mast cells. The characterising features of the invention will be evident from the following description and the appended claims . Detailed description of the invention The invention is based on the finding that mast cells can take up and store other types of amines, such as biogenic monoamines, besides histamine. This finding has lead to a completely new principle, upon which the invention is based, which may be described as "making the mast cell spit something out that is not histamine" . This principle involves the induced storage in mast cells, either competitive or non-competitive with histamine, of a "false mediator" molecule which lacks histaminergic ef- feet and which is released when the mast cell is triggered to secretion. This "false mediator" molecule is an amine, below called amine according to the invention. That mast cells have the capacity to take up, or form from their precursors, and store monoamines is a fact that has been known for quite some time but that has attracted surprisingly little attention. This property of the mast cells place them in the same category as nerve cells and certain neuroendocrine cells belonging to the so called chromaffin cell system. The monoamines seroto- nin (5-hydroxytryptamine) and dopamine act as neurotrans- mitters in certain regions of the central nervous system and are important issues in neuro- and psychopharmacol- cogic research. Histamine is synthesised by and stored in the mast cells of all mammalian species including man. Mast cells of some other species have also been reported to contain monoamines such as serotonin in the rat and mouse, and dopamine in cattle (cow and sheep), rabbit, hamster and cat (see Coupland and Heath: Journal of Endocrinology 22:71-76, 1961; Falck et al . Acta Pharmacologica (Kph) 21:51-58, 1964; Adams-Ray et al . Experientia 20:80-82, 1964, Journal of Pharmacy and Pharmacology 17:252-253, 1965) . Human mast cells normally appear to contain only histamine, but they have the capacity to take up serotonin, which has been indicated by the reported finding of this amine in mast cells situated close to a serotonin producing tumour (see Enerback L. , Nature (London) 197:610-611, 1963) . Rat mast cells normally contain 50 - 100 times more histamine than serotonin, both amines being stored in the secretory mast cell granules. In normal, unperturbed ani- mal, both amines are released very slowly from the cells with a half-life of about 30 days (see Wingren U. , et al . International Archives of Allergy and Applied Immunology 70:193-199, 1983). The mast cells can take up the serotonin precursor, 5-hydroxytryptophan, and convert it to se- rotonin which is stored in the granules (see Enerback L., Acta Pathgologica et Microbiologica Scandinavica 67:365- 379, 1966, and Enerback L., Gustafsson B., Histochemis- try, 53:193-202, 1977). In addition, the mast cells have a very efficient uptake mechanism for serotonin. If this amine is given to animals during a prolonged period of time it will be taken up in the granules and gradually displace histamine (see Wingren U. , et al . International Archives of Allergy and Applied Immunology 70:193-199, 1983) . These findings indicate that histamine and seroto- nin share storage and/or transport sites in the mast cells . Rat mast cells, which normally do not contain dopamine, can take up and store this amine after the administration of the amine or its precursor amino acid L-DOPA (see Rundquist et al . , Histochemical Journal 14:429-443, 1984) . Dopamine is stored in the granules but its storage does not affect or is affected by that of histamine or serotonin. In addition, the elimination of dopamine takes place more rapidly than that of the other two amines with an estimated half-life of 6 hours (see Rundquist et al . , Histochemical Journal 14:429-443, 1984). The uptake of both serotonin and dopamine can be prevented by the drug reserpin (see Enerback L., Acta Pathgologica et Microbiologica Scandinavica 67:365-379, 1966) , which also counteracts the uptake of these amines in nerve cells. In nerve cells and certain chromaffin cells, monoam- ine transporter proteins have now been identified. They carry out the transport of the monoamines over the cell membrane (dopamine transporter and serotonin transporter) as well as from the interior of the cell to the storage granules (vesicular monoamine transporter (VMAT) I and II) . Both a serotonin (reuptake) transporter (see Hoffman et al., Science, 254 (5031) :579-80, 1991) and a vesicular monoamine transporter (Erickson et al . , Proceedings of the National Academy of Sciences of the USA, 89 (22) : 10993-7, 1992) have been cloned from cultured mur- ine mast cells. The dopamine- and serotonin membrane transporters as well as VMAT II have recently been identified (although not yet published) at the protein level in the same mast cell line (RBL 2H3) by the inventors of the present invention. These facts taken together with the pharmacological in vivo findings described above show that the mast cells possess the machinery necessary for the uptake and storage of monoamines, much like nerve cells. As mentioned above the storage and transport of the substance according to the invention may be either competitive or non-competitive with histamine. In the case of competitive storage and transport, the substance ac- cording to the invention will compete with histamine with regards to transport means and/or binding sites in the mast cells resulting in the fact that histamine will be partly exchanged for the new agent that will be released together with histamine. The larger the amounts of the substance according to the invention stored, the smaller the amounts of histamine. Upon stimulation of the mast cells they will release both the substance according to the invention and histamine, but the released amount of histamine will be lower than normal since a part, or all, of it will be replaced by the substance according to the invention. The agent does not, in this case, have to be a histamine antagonist or have anti- inflammatory properties, although it may be advantageous if the substance according to the invention also has antihistaminic properties and/or other anti-inflammatory properties since the substance according to the invention will then coun- teract any allergic effects caused by the small amounts of released histamine. In the case of non-competitive storage and transport, the substance according to the invention is stored in the mast cells separately from histamine. This will not affect the storage of histamine, but the substance according to the invention will be released by the mast cells simultaneously with the release of histamine. In this case it is necessary for the substance according to the invention to be a histamine antagonist or have anti- inflammatory properties. Of course, competitive and non-competitive storage may also occur simultaneously. The term "substance according to the invention" refers to all amines suitable for use according to the in- vention, as well as to analogues, precursors and pharmaceutically acceptable salts of such amines and other similar substance that upon administration to a patient will be taken up by the mast cells, stored therein, and released therefrom when the patient is exposed to aller- gens; of course with the exception of histamine and any amines with histaminergic effects or any substance that in other ways increases the allergic response. The substance according to the invention is preferably a bio- genic monoamine or an analogue, a precursor or a pharma- ceutically acceptable salt thereof, and most preferably it is selected from the group consisting of dopamine and serotonin and metabolites, precursors, derivates and ana- logues thereof. The substance according to the invention may be either a naturally occurring amine, or a synthetically produces amine, or a metabolite, precursor, de- rivate or analogue thereof. Non-limiting examples of the substance according to the invention are 5- hydroxytryptophan (5-HTP) , α-metyl-DOPA (m-DOPA) and dopamine; the most preferred example being 5-HTP, as well as compounds comprising 5-HTP. Preferably, the substance according to the invention also has an antihistaminic ef- feet and/or an anti-inflammatory effect. Furthermore, it may be advantageous to combine administration of the substance according to the invention with administration of an anti -histamine drug. This may be done either by administering the two drugs separately or by administering them in the form of a preparation containing both drugs . It is also possible to produce a compound comprising a moiety consisting of a substance according to the invention and a histamine receptor blocking moiety. In such a product the substance according to the invention may constitute a core to which a histamine receptor blocking part is attached. The term "patient" used herein refers to a human or an animal in need of the treatment according to the in- vention, i.e. a human or an animal suffering from allergy or risking developing allergy. The pharmaceutical preparation according to the invention may either comprise the substance according to the invention itself, or a precursor or a pharmaceuti- cally acceptable salt or derivative thereof. The pharmaceutical preparation according to the invention may also comprise other substances, such as an inert vehicle, or pharmaceutically acceptable adjuvants, carriers, preservatives, etc., which are well known to persons skilled in the art. The effective dose of the substance according to the invention will vary depending on the substance used, and on the turnover rate of the substance in question. The suitable programme of treatment will vary, de- pending on factors such as the type of allergy the patent is suffering from, the type of substance used, turn-over time of drugs etc. For a patient suffering from hay fever a suitable treatment protocol may be as follows: treatment with daily repeated administrations of the pharma- ceutical preparation or the substance according to the invention during e.g. up to two to six weeks to load the storage sites of the mast cells; this is made before the allergy season, i.e. in the early spring in the case of hay fever, followed by maintenance treatment with less frequent intervals during the period the patient normally is suffering from the allergy. For patients with allergic disorders less well defined over time the period of maintenance treatment may be of longer duration. The invention is further illustrated in the follow- ing examples, which in no way are intended to limit the scope of the invention. Brief description of the drawings In the examples below, reference is made to the ap- pended drawings on which: Fig. 1 illustrates rat ear PCA responses in rats treated with subcutaneous injections of L-DOPA, m-DOPA, and 5-HTP compared to untreated rats (control) . The responses were evoked by passive immunization of one ear with anti-DNP IgE, followed by intravenous challenge 24 h later with DNP albumin together with a dye. The responses are expressed as the total absorbance from the sensitized minus that of the non- sensitized ear. Columns denote means of 7-20 rats, with S.E.-bars. Fig. 2 illustrates the effect of L-5-HTP injected subcutaneously 4 h before antigen challenge on rat ear PCA responses. Columns denote means of 5-11 rats, with S.E. -bars. Fig. 3 illustrates PCA-responses obtained as in Fig. 2 in rats given 50 mg/kg of L-5-HTP 4 h before antigen challenge (N=23) and in rats given 50 mg/kg of the 5-HTP decarboxylase inhibitor benerazide (BZ) 10 min before administration of 50 mg/kg of L-5-HTP 4 h before antigen challenge (N=ll) compared to a untreated group (control) (N=22) . Data are depicted as means with S.E. -bars. Examples In the examples the inventor of the present invention shows that the secretory function of mast cells can be modified by inducing an uptake and storage of mono- amines, which are capable of being released during the secretory response . For this purpose he used an experimental system based on a modified passive cutaneous anaphylaxis (PCA) reaction which is an equivalent to a an allergic reaction of immediate type in humans. Male Sprague-Dawley rats were passively immunized by the intradermal injection of monoclonal anti-DNP IgE into the right ear. Antigen challenge was performed 24 h later by the intravenous injection in a tail vein of DNP-albumin in a balanced salt so- lution containing the dye Evans blue. This dye binds to serum albumin and is therefore retained in the circulation during the conditions of the experiment. At the sensitized site in the left ear circulating DNP-antigen is bound to anti-DNP IgE molecules on the sensitized mast cells. This results in mast cell secretion with the release of mediator molecules including histamine, which cause increased vascular permeability with local swelling due to leakage of protein and fluid into the tissue. Under the conditions of this experiment the allergic reac- tion can be observed as a blue spot formed by the passage of albumin-bound dye through the walls of leaking micro- vessels. The rats were killed 30 min after the challenge and their ears removed. The dye was extracted from the tissue and the total absorbance measured. The PCA response was expressed as the total absorbance of the right (sensitized) ear minus the absorbance of the left (non- sensitized) ear (containing intravascular dye only) . The method measures the total allergic response resulting from the release of various mast cell mediators, not only mediators that are preformed and stored in the mast cells, such as histamine, but also mediators which are newly formed during the secretory response such as eico- sanoids. It also measures the possible modifying effects of other compounds that are released concomitantly with the natural mediators after storage in the mast cells as a result of pharmacological intervention. Example 1 Initially, the inventor studied the effect of the biogenic monoamines dopamine and serotonin on the PCA- response of mast cells because of the previously demon- strated capacity of mast cells to take up and store these amines (as mentioned above) . In the case of serotonin, the inventor and others have also demonstrated that this amine is released together with histamine during mast cell secretion (Berlin G and Enerback L. Agents and Ac- tions 18:89-91, 1986) . It is also know from previous studies that the mast cells can take up and decarboxylate also the precursor amino acids L-DOPA and L-5-HTP (Rundquist I. et al . , Histochemical Journal 14:429-443, 1975; Enerback L. and Jarlstedt J. Journal of Histochemistry and Cytochemistry 23:128-135, 1975). The inventor therefore used these precursors, rather than the amines themselves since they are less toxic and can be readily administered without harmful side effects both to animals and humans. The inventor also studied the amino acid α-methyl-DOPA, which is decarboxylated by the same enzyme (aromatic L-amino acid decarboxylase) , to α -methyl- dopamine and can be expected to be treated by the mast cells like the unsubstituted amino acid. 100 mg/kg of each amine precursor were administered 4 h before antigen challenge when the maximum uptake and storage of serotonin (Enerback L. and Jarlstedt J. Journal of Histochemistry and Cytochemistry 23:128-135, 1975) and dopamine (Rundquist I. et al . , Histochemical Journal 14:429-443, 1975) has taken place and the amino acids have been largely eliminated (Rundquist I. et al . , Histo- chemical Journal 14:429-443, 1975). The results are shown in Fig 1. In the figure L-DOPA is denoted by DOPA, and α-methyl-DOPA is denoted by m-DOPA. It was found that pre-treatment with DOPA, resulting in storage and release of dopamine, gave rise to an en- hanced PCA response while the uptake and subsequent release of serotonin resulting from the administration of its precursor amino acid 5-HTP significantly reduced the PCA response . Example 2 In this example the dose-response of administration of L- 5-HTP was studied. The experiment was performed as described above, with the difference that a 10 times higher anti-DNP-IgE concentration was used. The results are shown in Fig. 2. These results further demonstrate that the effect obtained according to the invention is dose dependent and that the PCA reaction can be practically abolished by pre-treatment with 5-HTP. Example 3 In this example the effect of benserazide, an inhibitor of aromatic amino acid decarboxylase, on the PCA- protection resulting from 5-HTP was studied. 50 mg/kg of benserazide was administered 10 min before administration of 50 mg/kg of L-5-HTP. The obtained PCR-response was compared to PCT-responses from rats treated with only L- 5-HTP, and from untreated rats, respectively. The experi- ment was in all other ways performed as described above. The results are shown in Fig. 3. The reduction of the PCA response by 5-HTP (P < 0.001) was partially prevented by pre-treatment with BZ (P < 0.01). The results clearly demonstrate that when benserazide is administered 10 min prior to 5-HTP, it significantly inhibits the protective effect of 5-HTP, which further supports that the observed effect is due to serotonin rather than to the precursor amino acid itself. These examples thus demonstrate that mast cells can be functionally modified by the pharmacologically induced storage of a biogenic monoamine, which is released during the allergic response. The storage can be brought about by the administration of its precursor amino acid. The results further show that 5-hydroxy-L-tryptohan (5-HTP) , the precursor of serotonin, is an effective anti- anaphylactic agent, preventing, in a dose dependent manner a passive cutaneous anaphylaxis reaction in rats, which is an equivalent to an immediate type allergic reaction in humans. This effect is comparable to that reported for a potent antihistamine drug, ketotifen, when tested in a similar system (Inagaki N. et al . , International Archives of Allergy and Applied Immunology 74: 91- 92,1984) . From the examples, it is evident that 5-HTP has a great potential interest as an anti-allergic agent in humans especially in view of its suggested mode of action, which is different from that of the commonly used anti- histaminics. The proposed mechanism of action represents an entirely new principle in that the drug in this case is decarboxylated and stored in the mast cells as a monoamine, which is released only when these cells are stimulated to secretion. The amine is therefore released strictly locally at the site of the allergic reaction and to an extent, which is proportional to, and regulated by, the degree of allergic response. For these reasons 5-HTP or a derivative of 5-HTP holds great promise as an antiallergic drug in humans, used alone or in combination with another antiallergic drug such as a histamine Hi- receptor blocker.

Claims: CLAIMS 1. A pharmaceutical preparation comprising at least one amine or an analogue, a precursor or a pharmaceuti- cally acceptable salt thereof capable of being taken up by and stored in mast cells and released therefrom upon binding of an allergen to a receptor on the mast cells, said amine not being histamine or an amine with hista- minergic effects. 2. A pharmaceutical preparation according to claim 1, wherein the uptake and storage of said amine, analogue, precursor or pharmaceutically acceptable salt upon administration to a patient will occur competitively with the storage of histamine. 3. A pharmaceutical preparation according to claim 2, wherein said amine, analogue, precursor or pharmaceutically acceptable salt has antihistaminic properties. 4. A pharmaceutical preparation according to claim 1, wherein said amine, analogue, precursor or pharmaceu- tically acceptable salt has antihistaminic properties, and the uptake and storage of said amine, analogue, precursor or pharmaceutically acceptable salt upon administration to a patient will occur non-competitively with the storage of histamine. 5. A pharmaceutical preparation according to any one of the claims 1-4, wherein said amine is a biogenic monoamine . 6. A pharmaceutical preparation according to claim 5, wherein said biogenic monoamine, analogue, precursor or pharmaceutically acceptable salt is selected from the group consisting of dopamine and serotonin and metabolites, precursors, derivates and analogues thereof. 7. A pharmaceutical preparation according to claim 6, wherein said biogenic monoamine precursor is 5-HTP. 8. A pharmaceutical preparation according to any one of claims 1-7, further comprising a histamine receptor blocking substance. 9. A pharmaceutical preparation according to any one of claims 1-8, further comprising an adjuvant. 10. A pharmaceutical preparation according to any one of claims 1-9, for treatment and/or prevention of al- lergy. 11. Use of at least one amine or an analogue, a precursor or a pharmaceutically acceptable salt thereof capable of being taken up by and stored in mast cells and released therefrom upon binding of an allergen to a re- ceptor on the mast cells for the production of a pharmaceutical preparation for treatment and/or prevention of allergy, said amine not being histamine or an amine with histaminergic effects. 12. Use according to claim 11, wherein the uptake and storage of said amine, analogue, precursor or pharmaceutically acceptable salt upon administration to a patient will occur competitively with the storage of histamine . 13. Use according to claim 12, wherein said amine, analogue, precursor or pharmaceutically acceptable salt has antihistaminic properties. 14. Use according to claim 11, wherein said amine, analogue, precursor or pharmaceutically acceptable salt has antihistaminic properties, and the uptake and storage of said amine, analogue, precursor or pharmaceutically acceptable salt upon administration to a patient will occur non-competitively with the storage of histamine. 15. Use according to any one of the claims 11-14, wherein said amine is a biogenic monoamine. 16. Use according to claim 15, wherein said biogenic monoamine, analogue, precursor or pharmaceutically acceptable salt is selected from the group consisting of dopamine and serotonin and metabolites, precursors, de- rivates and analogues thereof . 17. Use according to claim 16, wherein said biogenic monoamine precursor is 5-HTP. 18. Use according to any one of claims 11-17, wherein said pharmaceutical preparation further comprises a histamine receptor blocking substance. 19. A method for treatment and/or prevention of al- lergy, comprising administration to a patient of an effective amount of at least one amine or an analogue, a precursor or a pharmaceutically acceptable salt thereof, that is taken up by and stored in the patient's mast cells, and released therefrom upon binding of an allergen to a receptor on the mast cells, said amine not being histamine or an amine with histaminergic effects. 20. A method according to claim 19, wherein the uptake and storage of said amine, analogue, precursor or pharmaceutically acceptable salt occurs competitively with the storage of histamine. 21. A method according to claim 20, wherein said amine, analogue, precursor or pharmaceutically acceptable salt has antihistaminic properties. 22. A method according to claim 19, wherein said amine, analogue, precursor or pharmaceutically acceptable salt has antihistaminic properties, and the uptake and storage of said amine, analogue, precursor or pharmaceutically acceptable salt occurs non-competitively with the storage of histamine. 23. A method according to any one of the claims 19- 22, wherein said amine is a biogenic monoamine. 24. A method according to claim 23, wherein said biogenic monoamine, analogue, precursor or pharmaceutically acceptable salt is selected from the group consist- ing of dopamine and serotonin and metabolites, precursors, derivates and analogues thereof. 25. A pharmaceutical preparation according to claim 24, wherein said biogenic monoamine precursor is 5-HTP. 26. A method according to any one of claims 19-25, wherein said amine, analogue, precursor or pharmaceutically acceptable salt is administered in combination with a histamine receptor blocking substance.

Inventors: ENERBAECK LENNART, ENERBAECK, LENNART
Applicants: A & SCIENCE INVEST AB, ENERBAECK LENNART, A+ SCIENCE INVEST AB, ENERBAECK, LENNART
Application year: 1999
Main classification: A61K31
IPC codes: A61K31, A61P11, A61P37