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Purpose: To evaluate the effect of formulation variables on the bioadhesion and release properties of bioadhesive cyproheptadine hydrochloride tablets. Methods: Screening of polymers - hydroxypropyl methylcellulose, (HPMC), sodium carboxy methyl cellulose (CMC), and Carbopol 974p and 934p - in solution form were carried out by shear stress and detachment force measurement,based on Taguchi model, in order to determine their bioadhesion properties. Central composite design (CCD) was applied to optimize the combined effects of the polymers on release rate constant (K), diffusion coefficient (n), regression coefficient (R 2 ) and detachment force of a sustained release tablet formulation of cyproheptadine hydrochloride containing also a prompt dose of the drug. Results: The shear stress of 3 % solution of HPMC was greater than that of an equivalent concentration of Carbopol 934P. The values of K, n, R 2 and detachment force for the optimized formulation (F0) were 0.269, 0.696, 0.964 and 0.066 Newton (N), respectively, and showed good correlation with the predicted values, thus confirming the practicability and validity of the model. Conclusion: Gastric retention time can be increased for cyproheptadine hydrochloride by formulating it as a bioadhesive tablet that enhances the retention of the dosage form in the stomach and hence gastric absorption of the drug. Keywords: Cyproheptadine hydrochloride, Bioadhesive core tablet, Detachment force, Taguchi design, Central composite design

127 patients of urticaria were treated with chlorpheniramine maleate alone and in combination with cyproheptadine hydrochloride, ranitidine and doxepin and levamisole. Chlorpheniramine and doxepin combination showed a satisfactory result in 88.46% of patients. Overall study showed that a combination regimen is better than the antihistaminics alone. Drowsiness was the commonest side effect. Levamisole and chlorpheniramine maleate combination was found to be more effective than the antihimstamine alone.

A rapid high performance liquid chromatographic (HPLC) method for the determination of diltiazem hydrochloride, a calcium antagonist, is described. The stability indicating nature of the method was demonstrated by resolving diltiazem from products of decomposition. Reverse phase liquid chromatography was performed with an octadecyl silane-bonded silica column at ambient temperature, using UV detection at 240 nm. The mobile phase consisting of acetonitrile, methanol and 0.05 M monobasic potassium phosphate (25:20:55) was pumped at 2 ml/min. The internal standard was cyproheptadine hydrochloride. A percent RSD of > 1.5% and correlation coefficient 0.9996 were achieved over the concentration range studied (10–50 μg/ml.)

A new cyproheptadine hydrochloride (CHDHC1) ion selective F VC membrane electrode based on the ion-pair complex of CHDHC1 with sodium tetraphenylborate was prepared and its performance characteristics were studied. The electrode exhibited a Jinear response with a good Nernstian slope over a relatively wide range of concentration. Up to 21 days of continuous soaking, the calibration graph slope was constant at 57.1 mV/concentration decade, at 25°C, then it decreased as the time of soaking increases reaching 32.9 mV/decade after 37 days. The change in pH did not affect the electrode performance within the range 2–6. The standard electrode potentials were determined at different temperatures and used to calculate the isothermal coefficient of electrode. The electrode showed very good selectivity for CHDHC1 with respect to a large number of inorganic and organic cations. The standard addition method and potentiometric titration were used to determine (CHDHC1) in pure solution and in a. pharmaceutical...

In a hydrochloric acid medium, benzhexol hydrochloride, cyproheptadine hydrochloride, and maprotiline hydrochloride, can react with ammonium molybdate to form ion-association complexes by virtue of electrostatic attraction and hydrophobic interaction which result in a significant enhancement of the resonance light scattering intensity. The maximum scattering wavelengths were found at 364 nm, 364 nm, and 381 nm for benzhexol hydrochloride, cyproheptadine hydrochloride, and maprotiline hydrochloride systems, respectively. Spectral characteristics of the three systems, influencing factors, and optimum conditions were investigated. The reason of resonance light-scattering enhancement and the mechanism of interactions between the drugs and ammonium molybdate were also discussed. Based on the linear relationship between the enhanced intensity of resonance light scattering and the concentration of drugs, a highly sensitive method for the determination of the three drugs was developed, the detection limits being 0.0110 μmol L−1, 0.0038 μmol L−1, and 0.0155 μmol L−1 for benzhexol hydrochloride, cyproheptadine hydrochloride, and maprotiline hydrochloride, respectively. The method was successfully applied to the determination of the investigated drugs in pharmaceutical, serum, and urine samples.

We investigated the effects of several agents on the established itching model in NC/Nga mice, model of atopic dermatitis-like disease, to elucidate related characteristics. The number of spontaneous scratching behaviors (the duration time is over 1.5 s) by NC/Nga mice with severe skin lesions was measured before and after administration of agents for 24 h. The scratching behavior by NC/Nga mice was significantly suppressed by administration of dexamethasone or tacrolimus, but not by chlorpheniramine maleate or cyproheptadine hydrochloride. These results suggest that this method shows a good correlation with the effectiveness of drugs prescribed for itching in humans with atopic dermatitis, and histamine and serotonin do not play an important role in causing the scratching behavior seen by NC/Nga mice. The scratching behavior was also significantly suppressed by naloxone hydrochloride, dibucaine or capsaicin. These results suggest that the scratching behavior seen in this model is caused by itching signal transmission through neural system. Furthermore, we found that theophylline, pinacidil or limaprost had scratching suppression effects in this model.

Three methods are presented for the simultaneous determination of cyproheptadine hydrochloride (CP), thiamine hydrochloride (B1), riboflavin-5-phosphate sodium dihydrate (B2), nicotinamide (B3), pyridoxine hydrochloride (B6), and sorbic acid (SO). The chromatographic method depends on a high performance liquid chromatographic (HPLC) separation on a reversed-phase, RP 18 column. Elution was carried out with 0.1% methanolic hexane sulphonic acid sodium salt (solvent A) and 0.01 M phosphate buffer containing 0.1% hexane sulphonic acid sodium salt, adjusted to an apparent pH of 2.7 (solvent B). Gradient HPLC was used with the solvent ratio changed from 20:80 to 70:30 (over 9 min), then to 80:20 (over 11 min) for solvent A:B, respectively. Quantitation was achieved with UV detection at 220 and 288 nm based on peak area. The other two chemometric methods applied were principal component regression (PCR) and partial least squares (PLS). These approaches were successfully applied to quantify each drug in the mixture using the information included in the UV absorption spectra of appropriate solutions in the range 250–290 nm with the intervals �λ = 0.4 nm at 100 wavelengths. The chemometric methods do not require any separation step. The three methods were successfully applied to a pharmaceutical formulation and the results were compared with each other. © 2004 Elsevier B.V. All rights reserved.

Cyproheptadine (CY) has been used therapeutically as an appetite stimulant at a dose which appears to have antiserotoninergic activity. However, the role which CY may play in appetite regulation remains unclear. This study was designed to examine the effect of CY on ingestive behaviours in female Wistar rats. CY administered orally (0.52 mg kg-1 b.w., dissolved in the daily water) for up to six oestrus cycles did not affect 24 h food intake. On the other hand, CY reduced both 24 h liquid intake and 24 h urine output. Furthermore, 24 h liquid consumption and 24 h urine output, were found to fluctuate according to the oestrus cycle. Pharmacol Res

The inherent blood schizontocidal activities of five antihistaminic compounds, cyproheptadine hydrochloride (CYP), ketotifen hydrogen fumarate (KET), pizotyline hydrogen maleate (PIZ), azatadine maleate (AZAT) and loratadine (LOR) were examined against the following organisms: chloroquine-sensitive (CS) Plasmodium berghei and chloroquine-resistant (CR) P. yoelii ssp. NS in mice; and CS Tak 9 clone 96 and CR K1 strain of P. falciparum in vitro. Chloroquine, verapamil and desipramine were used as comparison standards. CYP, KET, PIZ were active against the CS strain in vivo with ED90 levels between 20 and 30 mg kg-1 (given sc daily for four days). They were slightly more active against the CR strain. AZA was active, but much less so than the other compounds. LOR, verapamil and desipramine were inactive in vivo at the doses tested. Against CS P. falciparum in vitro, all five antihistaminics and desipramine were active at EC50 concentrations ranging from about 50-80 mumol l-1, while verapamil was only active at 175 mumol l-1. Against the CR strain of this parasite, CYP, PIZ and LOR were slightly more active than against the CS strain, but KET, AZAT, desipramine and verapamil were significantly less active. The action of all these compounds in combination with chloroquine was then examined both in vivo and in vitro. The ability of verapamil and desipramine to reverse chloroquine resistance in vitro was confirmed, but only a low level of reversal was seen with these compounds in vivo. However, CYP, KET, PIZ and AZAT produced a marked reversal of chloroquine resistance both in vivo and in vitro. The implications of these observations in relation to further laboratory and clinical research are discussed.

A nuclear magnetic resonance and theoretical study on the conformations and molecular flexibility of cyproheptadine hydrochloride (1) is reported. In the 1H NMR spectrum of 1 in CDCl3, two conformational forms are observed to occur in an approximate ratio of 1:4. In both forms, NOE and coupling constant measurements suggested that the terminal N-methyl group is equatorial. NOE experiments identified the more populated conformer (labeled D) as similar to the form seen in the X-ray crystal structure of cyproheptadine. The other form observed (A) may in principle be converted to D via either inversion of the central ring (T(inv)) or concerted nitrogen (N(inv)) and piperidine ring inversion (P(inv)). Chemical-exchange peaks in the 400-MHz 2D NOESY/chemical-exchange spectrum suggested that the latter mechanism is responsible for interconversion between the two forms. A theoretical study of the various interconversion processes using both molecular mechanics (MM2) and molecular orbital (AM1) approaches is also reported.

Erythromelalgia is a rare disorder characterized by burning pain of the extremities associated with red discoloration and increased temperature of the skin. We observed the effects of several drugs on two patients with primary erythromelalgia. Anti-inflammatory drugs such as aspirin had no effects for their symptoms. The alpha-adrenergic agonist midodrine slightly reduced skin temperature and redness of the extremities, and minimally reduced the pain in one patient. The partial alpha-adrenergic agonist and 5-hydroxytryptamine (5-HT) agonist/antagonist dihydroergotamine transiently reduced skin temperature and pain to some degree in one patient. The 5-HT and histamine antagonist cyproheptadine effectively relieved the burning pain and increased skin temperature.

The clinical features and risk of hepatotoxicity of ‘Sleep-Qik’ (valerian dry extract 75 mg, hyoscine hydrobromide 0.25 mg, cyproheptadine hydrochloride 2 mg) were determined in 23 patients treated in our hospital between 1988 and 1991. The main clinical problems were central nervous system depression and anticholinergic poisoning. There was no clinical evidence of acute hepatitis in the 23 patients after taking an average of 2.5 g of valerian (range 0.5 to 12 g). There was no evidence of subclinical liver damage in 12 patients who had routine liver function tests performed approximately 6-12 hours after ingestion. Delayed onset of severe liver damage was excluded in 10 patients in whom a telephone follow-up was possible. However, subclinical liver dysfunction in the acute stage (onset after 12-24 hours) and in the intervening period after discharge from hospital could not be excluded. To establish the risk of hepatotoxicity in long-term users and in those taking an overdosage of valerian, a much larger study of longer duration with serial liver function tests is clearly needed.

Epidermolysis bullosa simplex—Dowling-Meara (EBS-DM) is a severe form of EBS, with oral and nail involvement as well as severe skin blistering. Reports1,2of treatment with 5-hydroxytryptamine—2 antagonists reducing the severity of blisters in subjects with EBS-DM prompted us to study cyproheptadine hydrochloride therapy in 13 individuals with a diagnosis of EBS-DM confirmed by electron microscopic examination. Participants served as their own controls. There was a 2-week observational period, an initial 6-week period during which cyproheptadine was taken daily, a 4-week period with no treatment, and a second 6-week regimen of daily administration of cyproheptadine. Standard dosages of cyproheptadine were used.3The study was designed in this manner in an attempt to compensate for temporal variation in blister formation as well as variations in season, weather, and activity levels of the participants. Subjects were asked to record the number of blisters lanced each day rather than the

The pH-solubility profiles of 3 pharmaceutical hydrochloride salts were determined in sodium acetate-hydrochloric acid buffer. Unusual pH-solubility profiles containing maxima at pH 4–6 were observed for phenazopyridine hydrochloride, cyproheptadine hydrochloride and bromhexine hydrochloride. The decrease in solubility at lower pH values was attributed to the common ion effect of chloride on the solubility product equilibrium of the hydrochloride salts. The dissolution behavior of the free bases and that of the hydrochloride salts of these drugs were compared in dilute hydrochloric acid solution, in pH range from 1.0 to 3.0. The apparent dissolution rates and solubilities of these hydrochlorides were less than those of the respective free base forms in the pH range of the stomach (pH 1.0–2.0). These results substantiated further the contention that the salt formation does not always result in an enhancement of solubility characteristics.

The mechanism of hypotension induced by petroleum ether seed extract of Croton penduliflorus (PEE-CP) was investigated in pentobarbital-anesthetized dogs and was compared with that of an official sample of Croton tiglium (PEE-CT). Prior treatment of the animals with mepyramine maleate and cyproheptadine hydrochloride did not modify the hypotensive activity of these extracts indicating the absence of histaminergic and serotoninergic mechanisms in the responses. When the animals were pretreated with atropine sulfate, the fall in blood pressure produced by intravenous injections of PEE-CP and PEE-CT was significantly decreased. Similarly, the PEE-CP and PEE-CT inhibited the responses to isoproterenol sulfate, a beta-adrenergic stimulant. In addition, propranolol hydrochloride effectively augmented the depressor effects of the seed extracts. The hypotensive effects of PEE-CP closely resembled those of PEE-CT. It is concluded that the hypotension produced by the seed extracts of Croton penduliflorus is...

In order to clarify the effects of cyproheptadine hydrochloride (Cyp) which is known clinically to stimulate the appetite and a subsequent increase in body weight, acute and chronic experiments were carried out. In the acute experiments, changes in single neuronal activity in the lateral area (LH) and ventromedial nucleus (VMH) in the rat hypothalamus by applications of Cyp, Na and Cl were studied by means of multibarreled electrodes. (1) About 60% of the VMH neurons were reduced in firing frequency by Cyp. Most of them were increased in frequency by glucose. (2) About 70% of the LH neurons were increased in frequency by Cyp. However, most of them were inihibited by glucose. (3) The activity of the Cyp sensitive neurons was modulated by stimulations of either the basolateral amygdaloid nucleus of the stria terminalis. (4) In the chronic experiments, food intake and body weight in young rats were significantly increased by Cyp. Thus, it was concluded that Cyp modulates both LH and VMH neurons which might account for its effects on feeding in children.

A 13-year-old female ingested an acute overdose of cyproheptadine hydrochloride (Periactin) and presented for treatment. She manifested all the classic signs and symptoms of an acute antihistamine overdose, including psychosis, except for miotic, minimally reactive pupils. The patient was supportively managed. All sequelae of the ingestion resolved within four days, and the child was released from the hospital. We discuss the unusual presentation of miotic pupils in an acute cyproheptadine overdose.

The effect of Periactin® on the rejection course was examined in 36 kidney allograft recipients. Half of the patients were given 32 mg of Periactin® daily as a supplement to the immunosuppressive treatment consisting of prednisone and azathioprine. The other half was given only the latter two medicaments. Rejection crises were treated with intravenous infusion with methylprednisolone. No beneficial effect of the Periactin® treatment was demonstrable. Graft survival and kidney functions thus did not differ between the two groups within the first 90 days after the transplantation. The frequency of rejection, on the other hand, was significantly higher in the group treated with Periactin®, especially within the first postoperative week. Periactin®, apparently, does not offer any advantage as a supplement to the immuno-suppressive treatment in human kidney transplantation.

Infusions of serotonin into a rat nervemuscle preparation decreased the force of the evoked twitch of anterior tibial and soleus muscles. Antiserotonin drugs (cyproheptadine hydrochloride, methysergide, chlorpromazine hydrochloride) prevented the adverse effect of serotonin if they were given prior to the serotonin infusion. These experiments support the hypothesis that serotonin may play a role in some diseases of muscle.

SUMMARY The effect of cyproheptadine hydrochloride on release of prolactin (PRL), growth hormone (GH) and cortisol following insulin-induced hypoglycaemia was investigated in a group of eight adult female and male subjects. The results of this study demonstrated that cyproheptadine does not influence the release of these three hormones under the conditions employed in this study. The conflicting observation concerning the action of cyproheptadine on pituitary function as reported in the literature, may be a reflection of the diversity of pharmacological actions of this drug. Thus, any purported influence this drug might have on pituitary hormonal release should be interpreted with caution.

A myopathy, which improved with cyproheptadine hydrochloride therapy, developed in a patient with carcinoid syndrome of ten years' duration. Biopsy examination revealed advanced atrophy of type II muscle fibers, with type I fiber preponderance. Many of the small fibers had degenerated. Carcinoid myopathy may be due to excess circulating serotonin.

• Patients with anorexia nervosa have concurrent problems of emaciation and depression. Therefore, treatment with medications affecting both weight gain and depression seemed reasonable. Seventy-two anorectic patients were randomly assigned in a double-blind study to receive cyproheptadine hydrochloride, a weight-inducing drug, amitriptyline hydrochloride, a tricyclic antidepressant, or placebo. Overall, cyproheptadine had a marginal effect on decreasing the number of days necessary to achieve a normal weight. There was a differential drug effect present in the bulimic subgroups of the anorectic patients: cyproheptadine significantly increased treatment efficiency for the nonbulimic patients and significantly impaired treatment efficiency for the bulimic patients when compared with the amitriptyline- and placebo-treated groups. The differential cyproheptadine effect on the anorectic bulimic subgroups is the first pharmacologic evidence of the validity of these subgroups. Cyproheptadine had an antidepressant effect demonstrated by a significant decrease in the Hamilton depression ratings.

A preliminary study of this size cannot resolve the question of the efficacy of a vasoactive amine antagonist in preventing serum sickness. Nor is it possible to fully assess patient compliance without use of an in–hospital setting. The incidence of serum sickness symptoms was six out of eight (75%) in treated patients; and three out of four (75%) In untreated patients; compared with an expected incidence of 74%. The incidence of significant illness is four out of eight (50%). Further study with a large group of patients would be needed to resolve this issue.

A reversed passive Arthus reaction was produced in guinea-pig knee joints by intravenous injection of ovalbumin and intra-articular injection of homologous anti-ovalbumin antiserum or specific IgG2 antibody. The optimum response was obtained by varying the concentration of antigen while keeping the amount of antibody constant. Joint swelling, leucocyte infiltration in the synovial fluid and joint pathology were measured 4–6 hours and 24 hours after initiation of the reaction. The PRA lesions were almost completely inhibited by complement or polymorphonuclear leucocyte depletion. The effects of a range of drugs on the 4–6 hours response were investigated following intraperitoneal or oral administration. Cyproheptadine hydrochloride, Trasylol, indomethacin, aspirin, phenylbutazone, prednisolone sodium phosphate, chloroquine diphosphate, SKF36914 (gold triethyl phosphine), cyclophosphamide, ketoprofen, sudoxicam and naproxen all reduced one or more of the symptoms of inflammation. However, cyproheptadine was only active at high and probably non-specific dose levels. D(−)penicillamine hydrochloride and mepyramine maleate were inactive.

Anaesthesia for abdominal surgery in a patient with carcinoid syndrome is reported. Pre-operative symptomatic improvement was obtained using cyproheptadine hydrochloride. Handling of the tumour and liver metastases, during surgery, produced signs of excess serotonin secretion which responded to intravenous methotrimeprazine.

Publisher Summary This chapter discusses a study to investigate the effect of trazodone and its metabolite, m-chlorophenylpiperazine (CPP), on acquisition of conditioned avoidance response. Male CD-1 mice were trained for conditioned avoidance response (CAR) in a shuttle-box apparatus. Each group consisted of 8 mice. The training comprised of 5 daily sessions of 100 trials each. CPP, 2 or 5 mg/kg (hydrochloride), was given 30 min before each session. Before CPP, the following drugs were given at times as indicated: cyproheptadine hydrochloride (CHD) 0.5 or 1 mg/kg, 30 min; alpha-methyl-p-tyrosine (AMT) 100 mg/kg, 90 min; pimozide (PMZ) 0.2 mg/kg, 60 min. All drugs were dissolved in 0.9% NaCl solution (saline), with the exception of PMZ, which was dissolved in 0.2% tartaric acid (vehicle). The controls received the solvent (10 ml/kg) at appropriate time intervals. All injections were given intraperitoneally. It was found that CHD did not antagonize the facilitatory action of CPP and in a dose of 1 mg/kg facilitated the CAR acquisition by itself. The effects of CPP and CHD were not additive.

Exposure of rat uterine horn suspended in de Jalon's solution, to Cyproheptadine hydrochloride (Cy) (10 μg/ml) inhibited response to prostaglandin E2 (20 ng/ml). The inhibition persisted even after removal of CY from the bath. Inhibition of response to E2 & F2α could be reversed by addition of calcium chloride to the bath. The extent of reversal was dependent on the concentration of calcium chloride. CY (10 μg/ml) completely inhibited contractile response to potassium free de Jalon's solution and partially inhibited cold contracture. These inhibitory actions could be reversed by addition of calcium chloride. CY was found to be a non-competitive antagonist of calcium. It is concluded that antagonism of CY to prostaglandins is due to its interference with entry of calcium into cytoplasm.

• Twenty-four-hour measurements of wrist and ankle kinetic energy expenditures were obtained on 20 hospitalized female anorectics during the first two weeks of their hospitalization. Kinetic energy was examined against measures of weight, depression, and Minnesota Multiphasic Personality Inventory scores in a regression analysis. Effect of cyproheptadine hydrochloride, amitriptyline hydrochloride, and placebo on activity was assessed. The results supported previous studies showing a positive relationship between weight gain and motor activity and challenge the commonly held notion that activity decreases in anorectics as their clinical condition improves. Motor activity was initially significantly suppressed by cyproheptadine and subsequently increased.

To the Editor.— In an earlier publication 1 we reported the effects of cyproheptadine hydrochloride on weight gain in 81 anorexia nervosa patients. Cyproheptadine is a serotonin and histamine antagonist with anticholinergic and sedative effects. Since that time, we have completed the full sample of 105 patients and have found that cyproheptadine affects characteristics of anorexia nervosa other than body weight. Females aged 10 to 40 years who met our study criteria for anorexia nervosa (an adaptation of those of Feighner et al 2 ) were entered into a pretreatment period of seven days in hospital, after which they were randomly allocated to groups receiving combinations of (1) cyproheptadine or placebo, and (2) behavior modification or its absence, and followed up on these treatments in the hospital for 35 days. Aside from body weight, patients were evaluated periodically on a variety of symptoms, behaviors, and attitudes. This design was repeated in

Cyproheptadine hydrochloride may be effective in controlling pruritus and in relieving seasonal and perennial pollinosis. With the exception of somnolence, which was usually transient, the adverse reactions reported from its use occurred infrequently.

Administration of cyproheptadine hydrochloride (5 mg/kg/day) to old rats for 48 days stimulated spermatogenesis. It also initiated spermatogenesis in the abdominal testis of unilaterally cryptorchid rats after a 15-day treatment.

A high-performance liquid chromatographic method is described which determines cyproheptadine hydrochloride in tablet formulations. Tablets were dissolved in water-acetonitrile (50:50) and analyzed using an octadecylsilane column with a mobile phase of 85% acetonitrile and 15% of an aqueous solution of 0.01 M 1-octanesulfonic acid, 0.5% triethylamine, and 1% acetic acid using UV absorbance detection at 280 nm.

• The addition of orally administered bromocriptine mesylate to cyproheptadine hydrochloride therapy completely normalized urinary-free cortisol levels for three months in a 21year-old woman with Cushing's syndrome in whom results from standard dexamethasone suppression and metyrapone stimulation tests as well as baseline corticotropin levels were originally compatible with a diagnosis of an occult pituitary adenoma. When transsphenoidal exploration of the sella turcica was unsuccessful and hypercortisolism persisted, the source of corticotropin was discovered using petrosal sinus and venal caval catheterization. A1 × 1.5-cm carcinoid tumor of the lung was identified and removed, thereby correcting the hypercortisolism. The tumor was demonstrated by immunoperoxidase staining to contain corticotropin. Orally administered bromocriptine, with or without cyproheptadine therapy, may be useful in the palliative treatment of some patients with carcinoid or other ectopic corticotropin-producing tumors. We postulate that bromocriptine therapy acted directly on carcinoid tumor cells to directly inhibit corticotropin production by a dopaminergic mechanism. ( Arch Intern Med 1987;147:989-991)

Sir. —It is well known that cyproheptadine hydrochloride (an antihistamine with serotonin-antagonistic activity) has an appetite-stimulating effect and promotes weight gain. 1, 2 However, its effect in promoting linear growth in association with weight gain often seems to be overlooked although it has been documented. 3-5 We therefore wish to report our observations during 29 months of cyproheptadine administration in a small-for-gestational-age female infant to reemphasize the usefulness of this low-cost drug therapy for growth enhancement. Patient Report. —A 4-year-old girl had been born normally to a 28-year-old woman after a 40-week gestational period. The infant's birth weight had been 2.32 kg ( At the age of 1

• Eight subjects with primary-acquired cold urticaria were treated with chlorpheniramine maleate, cyproheptadine hydrochloride, and placebo in a double-blind clinical trial. During three separate seven-day treatment periods, each patient took 4 mg of either active drug or lactose placebo three times a day. Objective measurements were made at the beginning and end of each treatment period by establishing the minimum time (MT) of cold stimulus application required to provoke urtication. In addition, the spontaneous appearance of cold urticaria lesions was recorded during each treatment period. The MT required for induction of urtication with a cold stimulus was significantly greater for eight patients receiving cyproheptadine as compared to chlorpheniramine or placebo (P ( Arch Dermatol 113:1375-1377, 1977)

CUSHING'S syndrome is usually treated surgically when it is associated with pituitary-dependent adrenocortical hyperplasia or an adrenal adenoma. However, the patient's general condition may exclude a surgical approach, and in these cases as well as in certain instances of Cushing's syndrome due to metastatic adrenal carcinoma of ectopic adrenocorticotropic hormone (ACTH) production, medical treatment has a place. The drugs available include mitotane, aminoglutethimide, and metyrapone; more recently, successful treatment of adrenocortical hyperplasia with cyproheptadine hydrochloride has been reported. Mitotane and aminoglutethimide have been the most commonly used, but both have a high incidence of adverse reactions. 1 Only mitotane leads to permanent destruction of the adrenal cortex. Spironolactone is commonly used in the management of the hypokalemia of Cushing's syndrome, but in the case we are presenting, it is suggested that this drug blocks the action of mitotane. Report of a Case A 65-year-old woman with features of florid Cushing's

In this case of sensitization to erythrocytes, painful purpuric nodules, evanescent neurological complaints, and abdominal pain developed in a patient three weeks after a traumatic ecchymosis. All hematologic and blood clotting studies were normal. Lesions could be reproduced locally by intradermal injections of either autologous whole red blood cells, autologus red blood cell stroma, or purified protein derivative (PPD) of tubercle bacilli, but they could not be reproduced by similar preparations of autologous red blood cell hemolysate, autologus plasma, histamine, calf-thymus deoxyribonucleic acid, salmon-sperm DNA, phosphatidyl-I-serine, or old tuberculin. The patient had an excellent response to cyproheptadine hydrochloride but later was free of lesions after spontaneously stopping treatment.