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Among the treatment modalities for ejaculatory disorders pharmacological treatment is the least invasive option. In this review, medical treatments for retrograde ejaculation (RE) and anejaculation (AE) are discussed systematically. Thirty-six studies dealing with patients with RE and 40 with AE evaluated the use of medical treatment and were included in this review. In addition four articles dealing with prostatic massage in anejaculatory patients were considered. Sperm quality in patients with retrograde and AE is often impaired. In patients with RE no differences in response to medical treatment could be detected between the different underlying diagnoses. Compared with ephedrine, imipramine and chlorpheniramine + phenylpropanalamine showed significantly higher reversal rates, while differences between the other treatments were not significant. Regarding the reversal of AE, the alpha agonistic drugs were significantly inferior to treatment with parasympathetic drugs. Of the different alpha agonistic medical treatments for the reversal of AE, milodrin showed significantly better rates than imipramine (p = 0.008), pseudoephidrine (p = 0.02) and ephedrine (p = 0.044), while all other treatments were not significantly different (p = 0.4). In conclusion, medical treatment for reversal of RE offers a realistic chance of conceiving offspring naturally and should be the treatment modality of first choice. In contrast, in AE, medical treatment cannot be recommended generally as treatment of first choice as it shows low overall success rates compared with electrovibration stimulation and electroejaculation. Under consideration of the mostly uncontrolled design of the majority of studies published, controlled clinical trials comparing different treatment options appear urgently warranted.

This was a double-blind, randomized, placebo-controlled, multicenter, parallel study comparing the effectiveness, at recommended doses, of an extended-release formulation of brompheniramine maleate and terfenadine in the treatment of allergic rhinitis. Subjects with symptoms of seasonal and/or perennial allergic rhinitis received brompheniramine 12 mg (n = 106), 8 mg (n = 105), terfenadine 60 mg (n = 106), or placebo (n = 53) twice daily for 14 days. On treatment days 3, 7, and 14, symptom severity ratings (i.e., rhinorrhea, sneezing, nasal congestion, itchy nose, eyes or throat, excessive tearing, postnasal drip) were completed by the physician; subjects and physicians each completed a global efficacy evaluation. Brompheniramine 12 mg and 8 mg and terfenadine were more effective than placebo (p < or = 0.05) on the physicians' global: brompheniramine 12 mg was more effective than terfenadine (p < or = 0.05) on days 7 and 14 and brompheniramine 8 mg on day 3. On the subjects' global evaluation, brompheniramine 12 mg and 8 mg and terfenadine were more effective than placebo (p < or = 0.05); brompheniramine 12 mg was more effective than terfenadine (p < or = 0.05) on days 7 and 14 and brompheniramine 8 mg on day 3. In general, brompheniramine 8 mg was comparable to terfenadine. On days 3 and 7, the total symptom and total nasal symptom severity scores for subjects receiving brompheniramine 12 mg were significantly more improved than for placebo (p < 0.05); terfenadine was not different from placebo; brompheniramine 12 mg was significantly better than terfenadine on day 7 (p < 0.05) for reducing total symptom severity and on days 3, 7, and 14 for reducing total nasal symptom severity. Adverse experiences were reported by 155 (41.9%) of the 370 subjects enrolled in the study. The overall rate of adverse experiences in the brompheniramine 12 mg treatment group (57.5%) was significantly greater (p < 0.05) than for brompheniramine 8 mg (38.1%), terfenadine (31.1%), and placebo (39.6%). In conclusion, an extended-release formulation of brompheniramine 12 mg or 8 mg bid alleviates allergic rhinitis symptoms and brompheniramine 12 mg provides significantly better relief of these symptoms than terfenadine 60 mg bid.

A double-blind, randomized, placebo-controlled, parallel-group, multicenter study was conducted to compare the effectiveness of an extended-release formulation of a classical antihistamine, brompheniramine, and a second-generation compound, loratadine, in the treatment of allergic rhinitis. Subjects with symptoms of allergic rhinitis received brompheniramine 12 mg twice daily (n = 112), loratadine 10 mg once daily (n = 112), or placebo twice daily (n = 114) for 7 days. Study medications were blinded using a double-dummy technique. Subjects completed an overall evaluation of symptom relief on a daily basis and returned on treatment days 3 and 7, at which times the investigator assessed symptom severity. The investigator and subject each completed a global efficacy evaluation, and subjects were interviewed regarding adverse experiences. The primary efficacy variable was the physicians' global efficacy evaluation on day 3. Symptoms also were analyzed as summed severity scores for all symptoms and for the nasal symptom cluster of rhinorrhea, sneezing, and nasal blockage. At all post-baseline evaluations (days 3, 7, and averaged over the two days), brompheniramine was significantly better than loratadine and placebo for both sets of summed symptom scores and all three global assessments. Loratadine was significantly better than placebo for physician ratings of total symptom severity averaged over the two days and for the physician and subject ratings of the nasal cluster on day 3. Central nervous system-related symptoms were the most frequently reported adverse experiences; somnolence was reported most frequently by patients taking brompheniramine, and its occurrence was less frequent as treatment continued. A nonprescription, extended-release formulation of brompheniramine 12 mg twice daily provided significantly better relief of symptomatic allergic rhinitis than loratadine 10 mg once daily.

We tested the efficacy of brompheniramine maleate in a large randomized, controlled trial of volunteers with experimental rhinovirus colds. Brompheniramine (12 mg) or placebo was administered at 8:00 A.M. and 8:00 P.M. for < or = 4 days after the onset of symptoms (24, 36, or 48 hours after virus challenge). During the first 3 days of treatment (the first 4 days after virus challenge), nasal secretion weights were lower for infected evaluable subjects receiving brompheniramine (n = 113) than for controls (day 1: 4.3 g vs. 6.8 g; day 2: 4.8 g vs. 7.7 g; and day 3: 3.3 g vs. 5.3 g) (P < or = .03), as were rhinorrhea scores (day 1: 0.6 vs. 0.8; day 2: 0.5 vs. 0.8; and day 3: 0.3 vs. 0.5) (P < .03), sneeze counts (day 1: 1.8 vs. 3.6; day 2: 2.1 vs. 5.1; and day 3: 1.3 vs. 3.3) (P < or = .001), and sneeze severity scores (day 1: 0.3 vs. 0.6; day 2: 0.25 vs. 0.7; and day 3: 0.2 vs. 0.4) (P < .001) (n = 112). Cough counts were lower after day 1 of treatment for the brompheniramine group than for controls (4.7 vs. 7.9) (P = .05) (day 2 after virus challenge), and other symptoms were modestly reduced or were unaffected in the brompheniramine group. Total symptom scores were also lower for the brompheniramine group than for controls on treatment days 1 (4.8 vs. 6.0) (P = .03) and 2 (4.1 vs. 5.6) (days 2 and 3 after virus challenge) (P = .003). Treatment with brompheniramine was associated with the adverse effects of somnolence (n = 3) and confusion (n = 1). Brompheniramine was efficacious treatment for the sneezing, rhinorrhea, and cough associated with rhinovirus colds.

Objective: To determine whether an antihistamine-decongestant combination (ADC) is superior to placebo in temporarily relieving symptoms of upper respiratory tract infection (URI) in preschool children., Design: Randomized, double-blind, placebo-controlled trial., Setting: Four pediatric offices in the Seattle, Wash, area., Participants: Children 6 months through 5 years of age with a URI of less than 7 days' duration., Methods: Children were randomly assigned to receive an ADC (brompheniramine maleate-phenylpropanolamine hydrochloride) or placebo as needed for URI symptoms. Two hours after each dose of study medication, changes in the child's runny nose, nasal congestion, cough, and sleep status were assessed by means of a standardized questionnaire., Results: A total of 175 responses were recorded for 59 patients. There were no statistically significant differences in symptom improvement between the ADC and the placebo group (runny nose, p = 0.48; nasal congestion, p = 0.94; cough, p = 0.66). However, the proportion of children asleep 2 hours after receiving the ADC was significantly higher than the proportion receiving placebo (46.6% vs 26.5%; p = 0.01). Results were unchanged after control for the correlated nature of repeated responses, age, symptom duration, use of acetaminophen, time that the medication was given, and parental desire for medication., Conclusions: The ADC was equivalent to placebo in providing temporary relief of URI symptoms in preschool children. However, the ADC did have significantly greater sedative effects than did placebo.

Background: Second-generation antihistamines, reported to lack central nervous system depressant activity, may be considered to have a clinical advantage over traditional antihistamines., Objective: To compare the effectiveness, at recommended doses, of an extended-release formulation of nonprescription brompheniramine and prescription terfenadine in the treatment of allergic rhinitis., Methods: This was a double-blind, randomized, placebo-controlled, multicenter, parallel study. Subjects with symptoms of allergic rhinitis received brompheniramine 12 mg (n = 96), terfenadine 60 mg (n = 96), or placebo (n = 95) twice daily for 14 days. Subjects returned on treatment days 3, 7, and 14; at which times, the investigator assessed symptom severity (i.e., rhinorrhea; sneezing; nasal blockage; pruritus of the eyes, nose, or pharynx; watery eyes; and postnasal drip). The investigator and the subject each completed a global efficacy evaluation, and subjects were interviewed regarding the occurrence of adverse experiences. Symptoms were analyzed as summed severity scores for (1) all symptoms and (2) for the symptom cluster of rhinorrhea, sneezing, and nasal blockage., Results: At all post-baseline evaluations (days 3, 7, and 14), brompheniramine was significantly better (P < or = .05) than terfenadine and placebo for both sets of summed symptom scores and for both global assessments. Terfenadine was significantly better (P < or = .05) than placebo on the physician's global at day 14. Central nervous system-related complaints were the most frequently reported adverse experiences among all three groups; somnolence was reported most frequently by brompheniramine-treated subjects., Conclusion: A nonprescription, extended-release formulation of brompheniramine, 12 mg bid, provided significantly better relief of symptomatic allergic rhinitis than terfenadine, 60 mg bid.

The efficacy and side effects of once-daily astemizole-D, a combination of 10 mg astemizole and 240 mg pseudoephedrine, were compared with those of twice-daily brompheniramine-D, a combination of 12 mg brompheniramine and 50 mg phenylpropanolamine (Lunerin), in 64 patients with seasonal allergic rhinitis caused by birch pollen. Efficacy was monitored by patient's diary scores, investigator assessments of nasal and eye symptoms and need of rescue medication during the 4-week study period. Both astemizole-D and brompheniramine-D reduced nasal and eye symptoms of allergy. There were no significant differences between the treatment groups regarding obstruction, but brompheniramine-D alleviated symptoms of rhinorrhoea and itchy eyes significantly more than astemizole-D. On the other hand, the patients in the brompheniramine-D group reported dry mouth, tiredness and drowsiness more often than those in the astemizole-D group. The results indicate that the two drugs are effective in the treatment of seasonal allergic rhinitis, but astemizole-D is better tolerated than brompheniramine-D.

We tested the hypothesis that antihistamine-decongestant combinations cause no clinically significant relief of the symptoms of upper respiratory tract infections in young children by randomly assigning 96 children to one of three treatment groups: antihistamine-decongestant, placebo, and no treatment. There were no differences among the three study groups in the proportion of children considered "better" overall by the parent 48 hours after the initial assessment (drug, 67%; placebo, 71%; no treatment, 57%; p = 0.53). There were no differences among groups in individual or composite symptom score changes. Two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms. In the proportion of parents believing that their child needed medicine, there was no difference between those who consented to participate and those who refused. Parents who wanted medicine at the initial visit reported more improvement at follow-up, regardless of whether the child received drug, placebo, or no treatment. We conclude that there is no clinically significant improvement in symptoms of upper respiratory tract infection, including no significant placebo effect, in young children for whom an antihistamine-decongestant is prescribed.

Ejaculation disorders in diabetic men are most frequently caused by retrograde ejaculation resulting from a damage of the sympathetic nerves at the level of the bladder neck. This results in incomplete or complete emission failure because of insufficient sperm transport. Diabetic ejaculatory sterility can be treated with anticholinergic drugs. The reported case shows that as a result of its antihistaminic and anticholinergic properties, brompheniramine can be successfully used in the treatment of men with diabetic ejaculatory sterility, particularly in patients with incomplete emission failure.

Zimelidine is a new antidepressant, which is structurally unrelated to the tricyclic and tetracyclic antidepressants. The pharmacological profile of zimelidine is different to that of other antidepressants in that it appears to owe the major part of its activity to the inhibition of serotonin uptake within the central nervous system. It appears that the demethylated metabolite, norzimelidine, may be responsible for most of the pharmacological activity. Studies to date suggest that zimelidine has overall efficacy comparable with that of amitriptyline, desipramine, maprotiline and doxepin in depressive illness, but at dosages which have achieved a similar overall clinical improvement zimelidine does not cause sedation, and anticholinergic side effects are mild and occur infrequently. Preliminary evidence suggests that zimelidine is effective against concomitant anxiety in depressed patients, and that it may also be useful in treating phobic anxiety. Zimelidine appears less likely to cause serious cardiotoxicity, in therapeutic dosages or an overdosage, than the tricyclic antidepressants, but it has not been studied in patients with cardiovascular disease. Sleep disturbance has occurred significantly more frequently during zimelidine therapy than during therapy with other sedative antidepressants, but whether this simply reflects the absence of sedation with zimelidine, or an effect on sleep as such, is presently unclear. Zimelidine appears to be effective and well tolerated in elderly patients. Thus, some aspects of the drug's profile (e.g. apparent low incidence of anticholinergic effects or drowsiness) may offer potential advantages in some patients; however, clinical experience with zimelidine to date has been limited, and further well designed studies are required to define the role of the drug more clearly in treating depressive illness compared with other antidepressants, and particularly to define whether some types of depression may respond more readily to zimelidine than to other antidepressants.

In a previous double-blind, 3-week study we compared the effect of clomipramine + placebo with clomipramine + tryptophan in 24 patients with endogenous depression. The patients in the latter group showed a significantly more rapid improvement than those in the former group, especially with regard to the depression-anxiety cluster of symptoms. These results prompted us to perform a similar study in which zimelidine, a more specific inhibitor of 5-HT reuptake, was used instead of clomipramine. In other respects the design was practically identical to that used in the previous study. Unexpectedly, tryptophan in combination with zimelidine, was not superior to placebo + zimelidine with respect to antidepressant activity. In comparison with the previous study, the antidepressant action of zimelidine showed no statistically significant difference from clomipramine. However, the patients tended to show a more prompt response after zimelidine + placebo than after clomipramine + placebo. The changes in CSF metabolites were likewise different in the two studies. In the two studies taken together 12 out of 49 patients showed prompt improvement within one week. This raises the question whether the therapeutic response to antidepressant drugs necessarily involves a delay as is generally assumed. Side effects were remarkably few and mild in the second study.

In a comparative evaluation of zimelidine, a potent serotonin (5-HT) uptake inhibitor, and desipramine, a potent noradrenaline (NA) uptake inhibitor, 65 hospitalized patients with endogenous depression were evaluated for the following biochemical variables: 5-HT uptake in platelets, 5-HT concentration in whole blood, inhibition of the 5-HT and NA accumulation in rat hypothalamic synaptosomes incubated in the patients' plasma, the excretion of 4-hydroxy-3-methoxyphenyl glycol (HMPG) in urine and the pretreatment levels of the amine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and HMPG in cerebrospinal fluid (CSF). results of the biochemical studies confirmed that zimelidine and desipramine have different profiles with respect to monoamine uptake. Thus zimelidine caused more marked inhibition of 5-HT uptake than desipramine, especially in rat brain synaptosomes incubated in the patient's plasma. Desipramine plasma was much more effective than zimelidine plasma in inhibiting NA uptake in the same preparation. The urinary excretion of HMPG decreased significantly during desipramine treatment but remained unchanged during zimelidine treatment. The combined clinical and biochemical results indicated that patients with low pretreatment levels of 5-HIAA and HVA in CSF responded significantly better to zimelidine than patients with high levels of 5-HIAA and HVA. On the other hand, patients with high levels of 5-HIAA and HVA. On the other hand, patients with high levels of HMPG in CSF tended to respond better to desipramine than those with low levels of this NA metabolite.

To evaluate the clinical efficacy, tolerance and pharmacokinetic properties of zimelidine in elderly people, twelve hospitalized depressed patients with a mean age of 80 years were included in a clinical trial. Zimelidine was administered twice daily at a dose of 50 mg during the first week, 75 mg during the second week and 100 mg during the third to sixty week. The patients also received a single oral test dose of 75 mg of zimelidine during an initial placebo week. All patients that completed the study improved according to the rating scales used. The drug was well tolerated, and adverse reactions were few and of mild or moderate severity. No influence of clinical importance was noted on hematology, liver and kidney functions, ECG, blood pressure or pulse rate. The mean elimination half-lives of zimelidine and norzimelidine were found to be 15 h and 35 h, respectively, which were longer than the half-lives earlier obtained in younger patients. The blood levels (AUC) in the geriatric patients were about twice those obtained earlier in healthy volunteers. The AUC values for both zimelidine and norzimelidine increased in close proportion to the increase in dose and, thus, the pharmacokinetics of zimelidine was apparently not dose-dependent in the dose interval used. The results obtained may indicate a reduction in the rate of metabolism for zimelidine in the elderly, possibly combined with increased total bioavailability of the drug. A reduction of the regular zimelidine dose may be recommended in the treatment of elderly patients.

In this single-blind study, the efficacy and safety of Disophrol Syrup was compared to Rinomar Syrup in seventy-eight paediatric patients with seasonal allergic rhinitis. Patients took 5-10 ml of the randomly assigned medication three to four times daily for a 2-week period. Severity of nasal obstruction, nasal secretion and mucosal swelling was graded and patient response to each week of therapy evaluated. An overall favourable response to Disophrol Syrup was observed in thirty-one out of thirty-five (89%) patients and in thirty out of thirty-five (86%) patients in the Rinomar group. No statistically significant difference in patient response to therapy between treatment groups was noted and no mentionable adverse reactions were reported.

The effects of brompheniramine maleate (12 mg twice daily in sustained release form) and terfenadine (60 mg twice daily) on the symptoms and well-being of 16 adults with urticaria with or without dermographism were assessed by symptom questionnaire. Following an initial 2-week period without therapy, each drug was taken for 2 weeks in a randomised double-blind cross-over study. Both drugs produced significant relief of itch and rash but only brompheniramine produced significant drowsiness. Brompheniramine maleate was more effective than terfenadine in the patients with dermographism.

The effect of a combined pediatric preparation of brompheniramine maleate and phenylpropanolaminehydrochloride (Lunerin mite) was studied in 17 children (aged 4-14 years) with allergic rhinitis. A double-blind cross-over technique was used, and a score system was used for evaluation of symptoms and signs. The results show that the drug had a good effect with statistical differences on the 1 per cent level between the active preparation and the placebo. The effect was less pronounced in children aged more than 10 years, for whom a higher dose of the drug is recommended. The frequency of side-effects was negligible.

Twenty-eight hospital inpatients with a primary major depressive disorder were treated with either zimelidine or placebo. Patients were matched for age, sex, and initial severity of depression and assigned double blind to the treatment regimen. An initial dosage of 150 mg/day was used for up to 6 weeks. Zimelidine was significantly more effective in alleviating the symptoms of depression than placebo, with 82% of zimelidine and 25% of placebo patients showing clinical improvement. There were few complaints of severe side effects in zimelidine-treated patients, and few effects on the cardiovascular system. Two zimelidine-treated patients were withdrawn for suspected drug-related adverse events. Zimelidine was a safe, effective antidepressant in this group of patients.

The retrograde ejaculation experienced by a juvenile diabetic man was successfully treated with brompheniramine, a drug having antihistaminic and anticholinergic properties. A possible mechanism of action is suggested.

A double-blind trial was carried out in 48 patients with allergic disorders to compare the efficacy and tolerance of mequitazine and brompheniramine. Patients received either 10 mg mequitazine or 24 mg brompheniramine daily, divided into 2 doses, for 14 days. The results, analyzed from patients' answers to a questionnaire recorded on a daily basis, showed that mequitazine was at least as effective as brompheniramine and caused significantly less drowsiness throughout the trial period. Few other side-effects were reported.

Effects of five antidepressant treatments--clorgyline, desipramine hydrochloride, electroconvulsive treatment, lithium carbonate, and zimelidine hydrochloride--on urinary outputs of dopamine, dihydroxyphenylacetic acid, and homovanillic acid (HVA) were investigated in unipolar and bipolar depressed patients. Clorgyline and lithium carbonate, which stabilized mood in bipolar patients, reduced the urinary output of HVA and whole-body dopamine turnover. Electroconvulsive treatment and zimelidine were without major effects, whereas desipramine had variable effects on these indexes of dopamine metabolism. Three patients, two receiving desipramine and one receiving clorgyline, who had increased HVA output during the drug treatments, became severely agitated and delusional.

This paper presents the results from a large multicenter study, performed at three clinical research units in the USA. Prior to a three to seven days of placebo washout period, patients were randomly assigned to zimelidine, a potent and selective 5-HT reuptake blocker, amitriptyline or placebo. The scheduled treatment period was four weeks. Dosage range was 75-300 mg/day for active medications. The rating instruments were the Hamilton Depression Scale and the Clinical Global Impression scale. The side effects were recorded by using a side effect inventory (TESS). Vital signs, laboratory work including clinical chemistry, ECG, and plasma levels of drugs, were performed. In the main efficacy evaluation there were 229 depressed outpatients included, all having completed at least two weeks of treatment after the washout period. The patients treated with zimelidine as well as those treated with amitriptyline showed a significant improvement relative to the placebo treated patients. For the safety evaluation 263 patients were included. Side effects, in particular anticholinergic effects but also drowsiness and cardiovascular effects, were much less pronounced in the zimelidine group as compared to the amitriptyline group. Only marginal differences regarding side effects were reported for zimelidine compared to those reported for placebo.

A partially-blind, three-way crossover study was carried out in 24 patients suffering from chronic urticaria to compare the efficacy and tolerance of brompheniramine maleate with that of clemastine fumarate. Patients received 4-week courses of treatment with 1 tablet twice daily of either 12 mg brompheniramine, 1 mg clemastine or placebo, in random order. Assessments were made by the physician of the patients' condition on entry and of response to treatment at the end of each 2-week period throughout the 12-week study period. At the end of the trial, patients were asked to state their preference, if any, for the different treatments. The results showed that both antihistamines were significantly effective compared to placebo and that at the dosage used brompheniramine was considered significantly better than clemastine in long-term control. Drowsiness was experienced by 4 patients whilst taking brompheniramine compared to 3 patients whilst taking clemastine. One patient experienced anorexia and vomiting with brompheniramine and 4 patients developed gastro-intestinal upsets whilst taking the placebo.

A comparative evaluation of zimelidine, a potent and selective serotonin (5-HT) uptake inhibitor, and desipramine, a potent noradrenaline (NA) uptake inhibitor, was carried out in a 4-week randomized, double-blind study in 65 hospitalized patients with endogenous depression. For evaluation of the clinical effect, Hamilton Rating Scale for depression (HRS) and a 14-item scale chosen from the Comprehensive Psychopathological Rating Scale (CPRS) were used. The concentration of drug in plasma was determined on the same days as the clinical ratings. There were no significant difference in the overall therapeutic effect between the two drugs. However, zimelidine had significantly better effect on anxiety. Although both agents were well tolerated, the zimelidine-treated patients reported significantly less severe anticholinergic side effects. Body weight did not change significantly in either treatment group. In the total material ther were no significant correlation between plasma concentrations of zimelidine, norzimelidine and desipramine and the amelioration score of either HRS and CPRS.

13 patients with endogenous depression, who had failed to obtain a lasting response to other antidepressant drugs or to electroconvulsive therapy, were treated with zimelidine. 3 showed a marked, and 3 a mild improvement. Side effects were minimal.

The major sleep characteristics of depression are summarized and new EEG sleep studies of antidepressants, including preliminary data on desipramine and zimelidine, are described. The relationship of steady-state plasma amitriptyline levels to REM sleep and the use of EEG sleep measures as predictors of clinical response to tricyclics will also be discussed. The effects of antidepressant agents on sleep are immediate and pronounced, and studies of these drug-induced effects may also represent a rational method for drug classification.

Seven patients who were diagnosed as suffering from phobic anxiety were treated with a new antidepressant which causes relatively selective inhibition of serotonin uptake. This compounds, zimelidine, was given for five weeks in doses of up to 300 mg per day. One patient dropped out of the study. Of the remaining six patients all but one made an improvement, which in most cases is thought to have been a drug effect. One patient relapsed some months following treatment and responded again to treatment with zimelidine having failed to respond to other psychotropic drugs.

A double-blind comparison between a combined antihistaminc and vasoconstricting preparation (Lunerin Mixture, Lunerin Mite) and placebo was performed in children with secretory otitis media. It was shown that the children given the active drug reacted more favourably on every investigated parameter (hearing threshold, appearance and mobility of the ear drum, number of myringotomies and observation time) than the patients who were given placebo. The incidence of side-effects was low.

A new antidepressant, zimelidine, which is a selective inhibitor of 5-HT-uptake, was tested in an open study of 13 patients, in each of whom the principal clinical diagnosis was phobic neurosis. The dose varied from 200 to 300 mg daily. After 6 weeks of treatment, 6 patients dropped out of the study as they were not appreciably improved, but 7 patients definitely improved and completed a treatment course of at least 12 weeks. In these cases it was possible to observe subjective relief of symptoms, improved social function, increased working capacity and a reduced need for anxiolytics. The effect appeared similar to the previously described effects of clomipramine treatment. The incidence of side effects was low and those that occurred were mild. Tolerance was assessed as very good by the great majority of patients. The study suggests that zimelidine has a favourable effect on mild, moderate, and even in some severe phobic conditions. Some comparisons with MAO-inhibitors were made. The results are sufficiently encouraging to suggest a controlled study.

In a seven-week double-blind crossover study, Disofrol (dexbrompheniramine maleate +d-isoephedrine sulphate) was compared with Lunerin (brompheniramine + 2-amino-1-phenyl-propanol-(1)-hydrochloride) and with placebo in the treatment of vasomotor rhinitis in thirty-one patients. From the patients' evaluations on diary cards Disofrol reduced the symptom running nose to a higher degree than Lunerin, an effect possibly ascribable to a greater anticholinergic activity. Both preparations had equal ability to relieve nasal blockage and both combinations were found to be more effective than placebo.

To determine whether the cough of the common cold arises from upper respiratory stimuli and whether antihistamine-decongestant therapy is an effective treatment for this cough, we prospectively evaluated volunteers with uncomplicated common colds in a randomized, double-blind, placebo-controlled study. After completing a standardized questionnaire and undergoing a physical examination, throat-culturing, and pulmonary function testing, subjects took the active drug or identical-appearing placebo for 7 days while they kept a diary in which they ranked the severity of 17 symptoms for 14 days. Pulmonary function testing was repeated, on average, on Days 4, 8, and 14. Forty-six percent of the variation in cough severity could be explained by throat-clearing and 47% of the variation in throat-clearing severity by postnasal drip. FIF50%, the only physiologic parameter that significantly correlated with cough, rose as cough severity fell. Antihistamine-decongestant therapy reduced postnasal drip and significantly decreased the severity of cough, nasal obstruction, nasal discharge, and throat-clearing during the first few days of the common cold. In addition, cough was 20 to 30% less prevalent in the active drug group within 3 days of starting therapy. We conclude that the cough of the common cold arose from upper respiratory tract stimuli and that cough and other cardinal symptoms of the common cold were reduced with antihistamine-decongestant therapy when these symptoms were at their worst.

A double-blind comparison of zimelidine, a potent and fairly selective 5-hydroxytryptamine (5-HT) uptake inhibitor, and desipramine, a noradrenaline (NA) uptake inhibitor, was carried out in hospitalized patients with endogenous depression. The patients were randomized into parallel groups receiving either zimelidine 100 mg b.i.d. or desipramine 75 mg b.i.d. Forty patients completed the study, twenty in each treatment group. Patients who did not respond adequately to one drug after 4 weeks were treated with the other drug (cross-over design) after a washout period. For evaluation of the therapeutic efficacy Hamilton Rating Scale for Depression, Comprehensive Psychopathological Rating Scale for Depression, Beck's Inventory and Global Rating Scales were used. All ratings indicated greater effectiveness for zimelidine as compared with desipramine, although the differences were not generally statistically significant. Only "somatic anxiety" on the Hamilton scale was significantly (P less than 0.05) in favour of zimelidine. Although both zimelidine and desipramine were well tolerated, the zimelidine patients reported significantly less severe anticholinergic adverse reactions. Of five patients who did not improve on zimelidine, three were then given desipramine but only one recovered completely. Of 10 patients who were switched over to zimelidine, 6 recovered completely and one moderately. Zimelidine produced strong inhibition of the uptake of 5-HT in platelets and a decrease in blood 5-HT after 2 weeks or longer treatment. The uptake of 5-HT in rat hypothalamic synaptosomes was reduced by about 50% and that of NA about 20% when incubated in the patients' plasma. All these effects seem to be mainly due to norzimelidine. Desipramine produced strong inhibition of the uptake of NA in hypothalamic synaptosomes but weak effect on the 5-HT uptake. Urinary MHPG tended to decrease during desipramine treatment but was not affected or tended to increase during zimelidine treatment.