MXPA01006105A - Use of apomorphine in the manufacture of a medicament for the treatment of organic erectile dysfunction in males - Google Patents

Abstract

A method of treating organic erectile dysfunction, particularly vasculogenic erectile dysfunction comprises administering to a male in need of such treatment a therapeutically effective amount of apomorphine or a pharmaceutically acceptable salt or pro-drug thereof.

Description

USE OF APOMORPHINE IN THE PREPARATION OF A MEDICINE FOR THE TREATMENT OF ORGANIC ERECTILE DYSFUNCTION IN MEN Field of the Invention The present invention relates to medical methods of treatment.

More particularly, the present invention concerns the use of apomorphine for the treatment of organic erectile dysfunction in men, particularly vasculogenic erectile dysfunction. Background of the Invention In the medical literature, the term imprecise "impotence" has been replaced by the term "erectile dysfunction". This term has been defined by the National Institutes of Health as the inability of man to achieve and maintain enough penile erection to allow satisfactory sexual intercourse. J. Am. Med. Assoc. 270 (1): 83-90 (1993). Because adequate arterial blood supply is critical for erection, any disorder that impairs blood flow can be implicated in the etiology of erectile deficiency. Erectile dysfunction affects millions of men and, although it is generally considered a benign disorder, it has a profound impact on their quality of life. However, it is recognized that in many men the psychological desire, the orgasmic capacity and the ability to ejaculate are intact even in the presence of erectile dysfunction. The etiological factors for erectile disorders have been classified as psychogenic or organic. Organic factors include those of a neurogenic origin and those of a vasculogenic origin. Neurogenic factors include, for example, lesions of somatic nerve trajectories which can damage reflexogenic erections and disrupt the tactile sensations necessary to maintain erections, and spinal cord injuries, which, depending on their location and severity, can produce several degrees of erectile deficiency. The psychogenic factors of erectile dysfunction include processes such as depression, anxiety and problems in the couple relationship which can damage erectile functioning by reducing erotic concentration, or otherwise, reducing awareness of the sensory experience. This can lead to an inability to start or maintain an erection. Vasculogenic risk factors include factors which affect blood flow and include cigarette smoking, diabetes mellitus, hypertension, vascular disease, high serum cholesterol levels, low levels of high density lipoprotein (HDL), and other disease conditions. Chronicles such as arthritis. The Masculine Male Aging Study (EEMM, as reported by HA Feldman and associates, J. Urol., 151: 54-61) discovered, for example, that the probability of complete erectile dysfunction by age was three times higher in subjects who report treated diabetes than in those without diabetes. Although there is some disagreement as to which of the many aspects of diabetes is the direct cause of erectile dysfunction, vascular disease is the most frequently mentioned.

The EEMM also found a significant correlation between erectile dysfunction and heart disease with two of its associated risk factors, hypertension and low serum high density lipoprotein (LAD). It was reported that 8-10% of all patients with untreated hypertension are impotent at the time they are diagnosed with hypertension. In the literature, the association of erectile dysfunction with vascular disease with strong hemodynamic impairments of erection demonstrated in patients with myocardial infarctions, coronary artery bypass surgery, cerebrovascular accidents and peripheral vascular disease is strong. The EEMM also found that cigarette smoking is an independent risk factor for vasculogenic erectile dysfunction; Finding that smoking cigarettes exacerbates the risk of erectile dysfunction associated with cardiovascular diseases. The treatment of erectile dysfunction varies, depending on the root causes of the condition in a particular patient. The form of treatment may include the use of psychotherapeutic, surgical, mechanical or pharmacotherapeutic methodology. Psychotherapeutic and / or behavioral therapy is usually useful for some patients with erectile dysfunction with non-obvious (psychogenic) organic causes. Venous litigation is effective in the treatment of patients who have difficulty maintaining an erection due to demonstrated venous leakage from the corpora cavernosa. Vacuum contraction devices are sometimes effective in generating and maintaining erections in patients with erectile dysfunction, and semi-rigid, malleable or inflatable penile prostheses are available for patients who fail or refuse other forms of therapy. Pharmacological agents that have been used in the treatment of erectile dysfunction, include vasodilators which are injected directly into the body of the penis, as well as agents administered orally. The most effective and well-studied injectable vasodilators are papaverine, phentolamine and alprostadil hydrochlorides, used singly or in combination. However, the use of penile vasodilators can be problematic in patients who can not tolerate transient hypotension. Agents administered orally include yohimbine, bromocriptine, fluoxetine, trazadone, trental, sildenafil, phentolamine, and ginkgoacea biloba extracts. US Pat. No. 5,770,606 describes the sublingual administration of apomorphine for the treatment of psychogenic erectile dysfunction in men. Apomorphine, a derivative of morphine, was first evaluated for use as a pharmacological agent as an emetic in 1869. In the first half of the 20th century, apomorphine was used as a sedative for psychiatric disturbances and as a behavioral altering agent for alcoholics and addicts. By 1967, the dopaminergic effects of apomorphine were observed, and the compound underwent intense evaluation for the treatment of Parkinson's. Since then, apomorphine has been classified as a selective dopamine receptor agonist, which stimulates the central nervous system producing an arousal response manifested by yawning and erection of the penis in animals and men. SUMMARY OF THE INVENTION It was found, according to the present invention, that the erectile dysfunction in a man can be effectively or minimally treated by administering to a man in need of such treatment a therapeutically effective amount of apomorphine or a salt, ester. or pharmaceutically acceptable prodrug thereof. In particular, organic erectile dysfunction having a vasculogenic origin is effectively treated by the oral administration of apomorphine. According to the present invention, apomorphine is administered in an amount sufficient to produce an effective penile erection, but insufficient to induce nausea, usually at doses that result in an amount sufficient to establish the plasma concentration levels of apomorphine, preferably fluctuating to approximately 5.5 nanograms / mL. The compound or one of its appropriate salts or pro-drugs can be administered alone or if needed at the upper end of the dose range, in combination with an anti-emetic agent. Detailed Description of the Invention. As used throughout this specification and the appended claims, the term "vasculogenic erectile dysfunction" refers to the condition whereby a man does not have the ability to initiate and / or maintain a sufficient erection of the penis for the Satisfactory intercourse due to the decrease in blood flow that accompanies a disease of the cardiovascular system and / or an associated risk factor. Such diseases include, but are not limited to, myocardial infarction, heart disease, peripheral vascular disease, impaired circulation resulting from diabetes, cigarette smoking, cardiac bypass surgery, and cerebrovascular accidents. Associated risk factors include hypertension, high serum low density lipoprotein (LBD) and low serum high density lipoprotein. The terms "acute dose" or "acute administration" mean the scheduled administration to the patient of a drug on a basis as needed. The term "co-administration" of two or more pharmacological agents means the administration of two or more agents together in single unit dosage form or, alternatively, in dosed forms of two or more units separately, one immediately following to the other. The terms "effective vasocongestive excitation" or "effective erection" means swelling or sufficient tumescence of the penis to effect vaginal penetration. The method of the treatment of the present invention includes the administration of apomorphine or one of its pharmaceutically acceptable acid addition salts, prodrug or prodrug ester to a patient suffering from vasculogenic erectile dysfunction. Apomorphine (f?,) - 5,6,6a, 7-tetrahydro-6-methyl- (4H) _debienzo [de, g] quinoline-10,11-diol, is a derivative of morphine obtained by means of the treatment of the latter with concentrated hydrochloric acid (L. Small and associates, J. Org. Chim., 5: 334 (1940) or by heating morphine with zinc chloride (Mayer, Ber., 4: 171 (1871)). It has the chemical structure: Apomorphine and contains a chiral center in position 6a. The total synthesis of the racemic mixture is reported by J. L. Neumeyer, et al., J. Farm, Scie., 59: 1850 (1970) and the synthesis of enantiomers separated by V. J. Ram and J. L. Neumeyer, J. Org. Chim., 46: 2830 (1981). The compound contains a basic nitrogen atom in the 6a position and therefore has the ability to exist in the free base form, as well as in acid addition salt forms. The compound can be administered as a free base or in the form of one of its more pharmaceutically acceptable salts or pro-drug derivatives. The administration of the racemic form, or any of the enantiomers, alone or in various combinations, is within the purpose of the present invention. As used in the present invention, the term "pharmaceutically acceptable salt" refers to those salts which are within the scope of the medical judgment expressed, suitable for use in contact with the tissues of human and lower animals without toxicity, irritation, response allergic and similar, and are consistent with the reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S.M. Berge, et al. Describes in detail pharmaceutically acceptable salts in the Pharmaceutical Sciences (J. Pharmaceutical Sciences) 66: 1-19 (1977). The salts are prepared in situ during the isolation and final purification of the compounds of the present invention, or separately by reacting the free base function with a suitable organic acid. Examples of pharmaceutically acceptable non-toxic acid addition salts are the amino group salts formed with inorganic acids such as hydrochloride acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid, or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid, or using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenosulfonate, benzoate, bisulfate, borate, butyrate, camforate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate. , hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3 phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, salts of valerate, and the like.

The term "pro-drug" refers to compounds that are rapidly transformed in vivo to produce the parent compound, such as, for example, by hydrolysis in blood. T. Higuchi and V. Stella provide a complete rationale for the pro-drug concept in "Pro-drug as New Supply Systems", (Pro-drugs as Novel Delivery Systems) Vol. 14 of the ACS Symposium Series, Chemical Society American (1975). Examples of esters useful as pro-drugs for compounds containing carboxyl groups can be found on pages 14-21"Bioreversible Transporters in Drug Design: Theory and Application" (Bioreversible Carriers in Drug Design: Theory and Apllication), edited by EB Roche, Pergamon Press (1987). The term "pro-drug ester group" refers to any of the many ester forming groups that are hydrolyzed under physiological conditions. Examples of prodrug ester groups include pivoyloxymethyl, acetoxymethyl, phthalidyl, indanyl and methoxymethyl, as well as other such groups known in the art. As used in the present invention, the term "pharmaceutically acceptable ester" of apomorphine refers to esters formed with one or both of the hydroxyl functions at positions 10 and 11, and which are hydrolyzed in vivo and include those that decompose easily in the human body to leave the parent compound or salt thereof. Suitable ester groups include, for example, those derived from pharmaceutically acceptable aliphatic carboxylic acids, particularly alkanoic, alkenoic, cycloalkanoic and alkanedioic acids, wherein each alkyl or alkenyl portion conveniently does not have more than 6 carbon atoms. Examples of particular esters include formats, acetates, propionates, butyrates, acrylates and ethylsuccinates. For an optimal response of vasocongestive excitation (erection) in man, the serum that circulates in stable state and the apomorphine levels of the midbrain tissue must be kept within a relatively defined defined range. The drug is preferably administered in a formulation which rapidly delivers the drug to the system, while maintaining and not exceeding the desired systemic levels of the drug. The methods known to the physician practicing the technique of pharmaceutical formulation can be used, which achieve this purpose. For example, the medicament can be delivered to the system by means of a solid oral formulation, by means of liquid formulation, including delivery with drops in sublingual form, by means of a tablet, lozenge or palette held in the mouth and absorbed orally. or sublingual; by means of a suppository formulation administered rectally; or by means of a powder, gel, or suspension, or an intranasal spray formulation. The medicament can also be administered in a sterile parenteral formulation by means of a subcutaneous or intramuscular route; however, sublingual, buccal, intranasal and suppository formulations are preferred because of their greater ease of administration and the greater potential that results for patient acceptance.

Dosage forms of sublingual apomorphine, which usually contain from about 2.5 to about 10 milligrams of apomorphine, are useful for treating the symptoms of vascular sexual dysfunction in man, including its symptomatic manifestations without nausea or other effects. undesirable collateral Apomorphine is administered in the period of time immediately prior to sexual intercourse, generally during the period from about 2 minutes and 1 20 minutes before intercourse, preferably during the period between about 2 minutes and about 60 minutes. minutes before sexual intercourse, so that sufficient levels of serum circulating predetermined and levels of apomorphine of the middle brain tissue during the period of sexual activity are maintained to induce and maintain adequate penile erection. during intercourse (eg, "effective vasocongestive excitation"), but less than the amount that causes nausea. Plasma concentrations of apomorphine are preferably maintained between about 0.3 to 5.5 nanograms per milliliter, preferably between about 0.3 to about 4 nanog branches per milliliter and more preferably between about 1 to about 2 nanog branches per milliliter. Apomorphine is a dopamine receptor agonist, which has a recognized use as an emetic when administered subcutaneously in approximately a dose of 5 milligrams. For the purposes of the present invention, apomorphine is administered in an amount sufficient to excite the cells in the middle brain region of the patient, albeit with minimal side effects. It is believed that this excitation of the cells is part of a cascade of stimulation that possibly includes neurotransmission with serotonin and oxytocin. Dopamine receptors in the middle brain region of a patient can be stimulated to a sufficient level to elicit an erectile response without inducing nausea, by administering apomorphine, preferably sublingual, in such a way that maintain a plasma concentration of apomorphine of no more than about 5.5 nanograms per m illiliter (5.5 ng / ml). The bling administration is usually carried out for a period of time in the range of from about 2 to about 10 minutes or more. The amount of apomorphine administered sublingually during this time period is preferably in the range of from about 25 micrograms per kilogram (μg / kg) of body weight to about 60 μg / kg of body weight. In patients sensitive to nausea, the onset of nausea can be prevented or delayed by supplying apomorphine in a range of controlled dilution, so as to provide serum levels in the circulation and apomorphine levels in the midbrain of the lower brain. 5.5 nanograms / mL. When apomorphine is administered at or near higher amounts of the aforementioned dose range, the likelihood of nausea onset can be reduced by concurrent administration of a ganglionic agent (ganglionic response inhibitor) such as nicotine or lobeline sulfate. For this purpose, the weight ratio of apomorphine of the ganglionic agent is in the range of from about 10 to about 1. Other antiemetic agents that can be used in conjunction with apomorphine are antidopaminergic agents such as metoclopramide, and phenothiazines, for example. example, chloropromazine, prochloroperazine, pipamazine, tiethylperazine, oxypendyl hydrochloride and the like. Also suitable are serotonin (5-hydroxytryptamine or 5-HT) antagonists, such as domperidone, ondansetron (commercially available as a hydrochloride salt under the designation Zofran ™), and the like; histamine antagonists such as buclizine hydrochloride, cyclizine hydrochloride, dimenhydrnanate (Dramamine ™), and the like; the parasympathetic depressants such as scopolamine and the like, as well as other antiemetics such as metopimazine, trimethobenzamide, benzauinamine hydrochloride, diphenidol hydrochloride and the like. Subsequently, preferred sublingual dose forms are shown in Table 1, Table I 150 milligram sublingual tablets of Apomorphine Hydrochloride 3-mg tablet Apomorphine hydrochloride 2.00 -% - P Mannitol 66.67 -% - P Ascorbic acid 3.33 -% - P Cítrico Acid 2.00 -% - P Avicel PH 102 15.00 -% - P Methocel E4 10.00 -% - P Aspartame 0.67 -% - P Magnesium Stearate 0.33 -% - P 4-mg tablet Apomorphine Hydrochloride 2.66 -% - P Mannitol 66.00 -% - P Ascorbic acid 3.33 -% - P Cítrico Acid 2.00 -% - P Avicel PH 102 15.00 -% - P Methocel E4M 10.00 -% - P Aspartame 0.67 -% - P Magnesium Stearate 0.33 -% - P -mg Tablet Apomorphine Hydrochloride 3.33 -% - P Mannitol 65.34 -% - P Ascorbic acid 3.33 -% - P Cítrico Acid 2.00 -% - P Avicel PH 102 15.00 -% - P Methocel E4M 10.00 -% - P Aspartame 0.67 -% - P Magnesium Stearate 0.33 -% - P If desired, and in order to facilitate absorption and thus availability, the presently contemplated dosage forms may also contain, in addition to excipients made in the form of a tablet, β-cyclodextrin or a β-cyclodextrin derivative as a hydride. Roxypropyl-β-cyclodextrin (HP BC D). Subsequently, dosage forms containing HPBCD are shown in Tables I and II.

Table II Sublingual Tablets of Apomorphine Hydrochloride with Hydroxypropyl- (beta) -Cyclodextrin Ingredient mg / Tab Aponnorfina Hydrochloride 4.0 HPBCD 5.0 Ascorbic acid 10.0 PEG 8000 39.5 Mannitol 39.5 Aspartame 2.0 TOTAL 100.00 Table III Sublingual Tablets of Apomorphine Hydrochloride with ß- Cyclodextrin Ingredient mg / Tab Apomorphine Hydrochloride 5.0 ß-Cyclodextrin 20.0 Ascorbic Acid 5.0 Mannitol 68.9 Magnesium Stearate 1.0 Aluminum Lacquer DíiC yellow 10 0.1 TOTAL 100.00 Dosage forms containing Nicotine and Domperidone are shown in Table IV, below Table IV Sublingual Tablets of Apomorphine Hydrochloride Containing an Anti-Emetic Agent Tablets containing Nicotine Ingredient mg / Tab Apomorphine Hydrochloride 5.0 Ascorbic Acid 5.0 Mannitol 67.9 Magnesium Stearate 1.0 Nicotine 1.0 ß-Cyclodextrin 20.0 D &C Yellow Aluminum Lacquer 0.10 TOTAL 100.0 Tablets containing Domperidone Ingredient mg / Tab Apomorphine Hydrochloride 5.0 Ascorbic Acid 5.0 Mannitol 58.9 Magnesium Stearate 1.0 Domperidone 10.0 ß-Cyclodextrin 20.0 Aluminum Lacquer D &C Yellow 10 0.1 TOTAL 100.00 Preferred sublingual dosage forms are dissolved within a period of time less than about 10 m in. The dissolution time can be essentially instantaneous or, if desired, so long as to maintain the required plasma concentration of apomorphine. Preferably, the dissolution time in water for the presently contemplated dosage forms is from about 3 minutes to about 5 minutes. A 3-branch, double-blind, randomized, placebo-controlled, multi-center study was conducted in patients diagnosed with male erectile dysfunction. For each sequence, patients received a placebo in one of the treatment periods, and a dosage (2mg, 4mg, 5mg, or 6mg) of apomorphine in the other treatment period. This treatment resulted in approximately one third of the patients who received one of the three doses of apomorphine.

During the study treatment periods, patients and their sexual partners were instructed to try intercourse at least twice a week. Each time the study medication was taken, the patient completed a questionnaire and mailed it to the study sponsor. The questionnaire recorded the date and time the study medication was taken, an evaluation of the erection whether sexual intercourse has occurred or not, and the satisfaction associated with each attempt. The patient also completed a diary which recorded the latency and duration of erections associated with the use of the study drug and antiemetic and use of concomitant medication and any adverse effects. If an erection arose after the administration of the study medication to the patient, the duration of the erection and the time to achieve an erection were recorded in the patient's diary. The data from these studies were analyzed, and the results of patients who were diagnosed as hypertensive or who were taking a medication for hypertension were tabulated. These results of the study appear in Tables V to V, below. Table V shows the responses of study participants who received placebo or one of four dosages (2mg, 4mg, 5mg, or 6mg) of apomorphine with respect to the questionnaire question "Did you achieve an erection firm enough for intercourse? ? " Table V Erection Sufficiently Firm for Sexual Contact (Based on Attempts) Apomorphine Placebo Dosage No. of Patients Response Attempts (Percentage) Attempts (Percentage) Value P 2mg 65 S Yes 2 21100 4 433..3300 1 16622 3 344..1111 0.028 2mg No 275 56.70 309 65.61 4mg 53 S Yes 2 20022 5 522..6600 1 10055 2 277..0066 < 0.001 4mg No 182 47.40 283 72.94 5mg 26 SSií 9955 4499..4488 6622 3300..8855 0.022 5mg No 97 50.52 139 69.15 6mg 50 SSíí 223333 6622..1133 111199 3322..9966 < 0.001 6mg No 142 37.87 242 67.04 The data in Table V show that apomorphine, tested in each dosage, significantly increases the percentage of reported erections, which were firm enough for intercourse. Although without adhering to one theory to the exclusion of others, it is believed that the slightly low "yes" answers for the 5 mg dosage, when compared to the 4 mg dosage, reflect the smallest population of patients for the dosing study. of 5 mg. Table VI shows the "success" responses to the questionnaire of study participants who received placebo or a four-dose (2 mg, 4 mg, 5 mg, or 6 mg) apomorphine. A treatment is considered to be a "success" for the patient if at least 50% of the first eight attempts, while the treatment was used, resulted in erections strong enough for intercourse. Table VI shows the percentage of patients classified as successful treatment. The results show the success ranges of 68.0% for the medication versus 38.8% for the placebo in the 6 mg medication dosage; 53.8% for the medication versus 38.5% for the placebo in the 5 mg medication dosage; 62.3% for the medication against Table VI "Successful" Erections Sufficiently Firm for Sexual Contact 26. 9% for placebo in the 4 mg drug dose; and 44.6% for the medication versus 38.5% for the placebo at the 2 mg drug dose. The results were statistically significant for the dosages of 4 mg and 6 mg; although they showed a favorable range of success for dosages of 2 mg and 5mg; the statistical insignificance is possibly due to the small size of the sample. Finally, Table VII shows the results of the number of attempts which actually resulted in intercourse as reported by the study participants in the questionnaire.

Table VII Attempt that Resulted in Sexual Contact (Exposed in the First Eight Attempts) Apomorphine Placebo Dosage No. of Patients Response Attempts (Percentage) Attempts (Percentage) Value P 2mg 65 S Yes- 1 18855 3 388..2222 1 14488 3 311..3366 0.080 2mg No 299 61.78 324 68.64 4mg 52 S Yes 1 18833 4 477..6666 8 877 2 222..9966 O.001 4mg No 201 52.34 292 77.04 5mg 26 SSIí 110000 5522..0088 6622 3300..8855 0.012 5mg No 92 47.92 140 69.65 6mg 50 SSíí 220055 5566..0011 9966 2266..6677 < 0.001 6mg No 161 43.99 264 73.33 An attempt was defined as the administration of the study medication and the filling of the question of efficacy in the corresponding questionnaire.

The results presented in Table VII parallel to those in Table V, with the percentage of attempts which resulted in coitus being 56.01% for the drug versus 26.67% for the placebo in the dosage of the 6 mg drug; 52.08% for the drug versus 30.35% for the placebo in the 5 mg drug dosage; 47.66% for the drug versus 22.96% for the placebo in the 4 mg drug dosage; and 38.22% for the drug versus 31.36% for the placebo in the dosing of the 2 mg medicine. The data presented in the Tables from V to VII show that the administration of apomorphine to men suffering from hypertension, a representative vasculogenic cause for erectile dysfunction, is successful treatment or reduction of the condition. Although the embodiments of the present invention that are believed to be preferred have been shown and described, it will be clear to one skilled in the art that various modifications may be made to the practice of the present invention without departing from its scope as defined in attached claims.

Claims (13)

1. R E I V I N D I C A C I O N S 1. A method for treating organic erectile dysfunction in a man, comprising administering to said man in need of such treatment, a therapeutically effective amount of apomorphine or a pharmaceutically acceptable salt, ester, or prodrug thereof.
2. 2. The method according to claim 1, wherein said erectile organic dysfunction is of vasculogenic origin relative to a disease of the cardiovascular system.
3. 3. The method according to claim 1, wherein said erectile dysfunction is of vasculogenic origin relative to a risk factor associated with a disease of the cardiovascular system.
4. 4. The method according to claim 2, wherein said disease of the cardiovascular system is myocardial infarction, heart disease or peripheral vascular disease.
5. 5. The method according to claim 2, wherein said disease of the cardiovascular system, is impaired circulation associated with diabetes, cardiac bypass surgery, cerebral vascular trauma or cigarette smoking.
6. 6. The method according to claim 3, wherein said risk factor associated with a disease of the cardiovascular system is hypertension, high serum low density lipoprotein (LBD) and low serum high density lipoprotein (LAD).
7. 7. The method according to claim 1, wherein said apomorphine is administered in an amount sufficient to produce an effective erection of the penis in said man, but insufficient to induce nausea. The method according to claim 1, wherein said apomorphine is coadministered with an effective inhibitory amount of vomit of an antiemetic agent. 9. The method according to claim 1 wherein said apomorphine is administered in an amount between about 25 micrograms / kg of body weight and between about 60 micrograms / kg of body weight. The method according to claim 1, wherein said apomorphine is administered in an amount sufficient to establish plasma concentration levels of apomorphine, ranging from about 0.3 to about 5.5 nanograms / mL. The method according to claim 10, wherein said plasma levels of apomorphine range from about 0.3 to about 4 nanograms / mL. The method according to claim 11, wherein said plasma levels of apomorphine range from about 1 to about 2 nanograms / mL. The method according to claim 8, wherein said antiemetic agent is selected from a group consisting of nicotine, lobeline sulfate, metoclopramide, chloropromazine, prochloroperazine, pipamazine, thiethylperazine, oxypendyl hydrochloride, domperidone, ondansetron, hydrochloride buclizine, cyclizine hydrochloride, dimenhydrinate, scopolamine, metopimazine, trimethobenzamide, benzauinamine hydrochloride and diphenidol hydrochloride. . A method for treating erectile dysfunction in a hypertensive man, comprising administering to said man in need of such treatment, a therapeutically effective amount of apomorphine or a pharmaceutically acceptable salt, ester or prodrug thereof. . The method according to claim 14, wherein said apomorphine is coadministered with an effective inhibitory amount of the vomit of an antiemetic agent. The method according to claim 14, wherein said apomorphine is administered in an amount between about 25 micrograms / kg of body weight and about 60 micrograms / kg of body weight. The method according to claim 14, wherein said apomorphine is administered in an amount sufficient to establish plasma concentration levels of apomorphine, ranging from about 0.3 to about 5.5 nanograms / mL. The method according to claim 17, wherein said plasma levels of apomorphine range from about 0.3 to about 4 nanograms / mL. The method according to claim 18, wherein said plasma levels of apomorphine range from about 1 to about 2 nanograms / mL. The method according to claim 15 wherein said antiemetic agent is selected from a group consisting of nicotine, lobeline sulfate, metoclopramide, chloropromazine, prochloroperazine, pipamazine, tiethylperazine, oxypendyl hydrochloride, domperidone, ondansetron, buclizine hydrochloride, hydrochloride of cyclizine, dimenhydrinate, scopolamine, metopimazine, trimethobenzamide, benzauinamine hydrochloride and diphenidol hydrochloride.