piperidines and diphenylpyraline

In a double-blind study, diphenylpyraline (Lergobine) was given to 63 patients whose main symptoms were stuffiness of the nose, increased secretion of mucus, snuffling, sneezing and redness of the eyes. Fifty-seven patients were given placebo for identical symptoms. Diphenylpyraline was found to have a better effect on all the symptoms than placebo. The difference was statistically significant in respect of the discharge of mucus and redness of the eyes, and when the total symptoms were considered as a whole. In atopic patients the better effect of diphenylpyraline was highly significant.

Topics: Adolescent; Adult; Benzhydryl Compounds; Child; Clinical Trials as Topic; Delayed-Action Preparations; Drug Evaluation; Female; Histamine H1 Antagonists; Humans; Hypersensitivity, Immediate; Male; Middle Aged; Piperidines; Placebos; Rhinitis, Allergic, Seasonal; Skin Tests

Patch testing is essential for identification of culprits causing allergic contact dermatitis.. We sought to identify trends and allergen changes in our standard series during 2006 to 2010, compared with our previous report (2001-2005).. We conducted a retrospective review of patch-test results.. A total of 3115 patients were tested with a mean of 73.0 allergens. Since our prior report, 8 allergens were added to the standard series; 14 were deleted. Significantly higher rates of allergic positive reaction were documented for carba mix, 3%, and Disperse Orange 3, 1%. Rates were lower for 10 allergens: neomycin sulfate, 20%; gold sodium thiosulfate, 0.5%; hexahydro-1,3,5-tris(2-hydroxyethyl)triazine, 1%; disperse blue 124, 1%; disperse blue 106, 1%; diazolidinyl urea, 1%; hexylresorcinol, 0.25%; diazolidinyl urea, 1% aqueous; 2-bromo-2-nitropropane-1,3-diol, 0.25%; and lidocaine, 5%. Many final patch-test readings for many allergens were categorized as mild reactions (erythema only). Overall allergenicity and irritancy rates declined significantly since our prior report. Results were generally comparable with those in a North American Contact Dermatitis Group report from 2005 to 2006.. This was a retrospective study; there is a lack of long-term follow-up.. Since our previous report, our standard series composition has changed, and overall rates of allergenicity and irritancy have decreased. Notably, many final patch-test readings showed mild reactions.

Topics: Academic Medical Centers; Adult; Aged; Allergens; Azo Compounds; Cohort Studies; Dermatitis, Allergic Contact; Female; Gold Sodium Thiosulfate; Humans; Male; Middle Aged; Minnesota; Nitroparaffins; Patch Tests; Piperidines; Propane; Reference Standards; Retrospective Studies; Sensitivity and Specificity; Young Adult

Diphenylpyraline hydrochloride (DPP) is an internationally available antihistamine that produces therapeutic antiallergic effects by binding to histamine H₁ receptors. The complete neuropharmacological and behavioral profile of DPP, however, remains uncharacterized. Here we describe studies that suggest DPP may fit the profile of a potential agonist replacement medication for cocaine addiction. Aside from producing the desired histamine reducing effects, many antihistamines can also elicit psychomotor activation and reward, both of which are associated with increased dopamine concentrations in the nucleus accumbens (NAc). The primary aim of this study was to investigate the potential ability of DPP to inhibit the dopamine transporter, thereby leading to elevated dopamine concentrations in the NAc in a manner similar to cocaine and other psychostimulants. The psychomotor activating and rewarding effects of DPP were also investigated. For comparative purposes cocaine, a known dopamine transporter inhibitor, psychostimulant and drug of abuse, was used as a positive control. As predicted, both cocaine (15 mg/kg) and an equimolar dose of DPP (14 mg/kg) significantly inhibited dopamine uptake in the NAc in vivo and produced locomotor activation, although the time-course of pharmacological effects of the two drugs was different. In comparison to cocaine, DPP showed a prolonged effect on dopamine uptake and locomotion. Furthermore, cocaine, but not DPP, produced significant conditioned place preference, a measure of drug reward. The finding that DPP functions as a potent dopamine uptake inhibitor without producing significant rewarding effects suggests that DPP merits further study as a potential candidate as an agonist pharmacotherapy for cocaine addiction.

Topics: Animals; Behavior, Animal; Benztropine; Central Nervous System Stimulants; Cocaine; Cocaine-Related Disorders; Dopamine Uptake Inhibitors; Exploratory Behavior; Histamine H1 Antagonists; Illicit Drugs; Kinetics; Male; Mice; Mice, Inbred C57BL; Motor Activity; Nucleus Accumbens; Piperidines; Psychomotor Agitation; Reward; Spatial Behavior

2-Substituted derivatives of diphenylpyraline and their 1-phenyl and 1-phenethyl analogues have been prepared in several steps from dihydropyridine-2(1H)-thiones. The structures of all new compounds have been confirmed by NMR spectroscopy. Their activity against Mycobacterium tuberculosis H(37)Rv as well as their cytotoxicity against human cells (HEK-293) have been determined via in vitro assays. The antimycobacterial potency was in general increased by substitution in ring position 2. The most promising modifications were a 2-isopropyl derivative and a 1,2-diphenyl analogue.

Topics: Antitubercular Agents; Cell Proliferation; Cells, Cultured; Kidney; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis; Piperidines; Structure-Activity Relationship

Diphenylpyraline hydrochloride (DPP) is used clinically as an antihistamine drug, but its neurobiological effects are not completely understood. Voltammetry and microdialysis were used to investigate potential actions of DPP on the dopamine system. Voltammetric monitoring of dopamine signals in mouse nucleus accumbens slices showed that DPP (10 microM) markedly inhibited dopamine uptake. There was a 20-fold increase in apparent Km for dopamine uptake, while Vmax was unchanged. Microdialysis experiments demonstrated that DPP (5 mg/kg, i.p.) elevated extracellular dopamine levels (approximately 200%) in mouse nucleus accumbens. DPP (5 and 10 mg/kg) also induced locomotor activation. All of the effects of DPP were comparable with those of cocaine. Taken together, these results indicate that DPP acts as a competitive dopamine transporter inhibitor similar to cocaine.

Topics: Animals; Central Nervous System Stimulants; Female; Histamine H1 Antagonists; Male; Mice; Mice, Inbred C57BL; Motor Activity; Piperidines; Receptors, Histamine H1

A long-term follow-up study was made of three patients with cerebrotendinous xanthomatosis (CTX) associated with parkinsonism, two of whom were siblings. Besides typical CTX symptoms, all three patients showed severe parkinsonism. This observation has been rarely reported in CTX. The fact that the two siblings showed parkinsonism strongly suggests the genetic propensity to parkinsonism in these CTX patients. Positron emission tomography studies of the two patients revealed presynaptic dysfunction of the nigro-striatal dopaminergic system. Treatment with the reductase inhibitor hydroxymethyl glutaryl coenzyme successfully corrected the serum cholestanol level in the early stage of the disease, which, however, did not arrest the progression of clinical symptoms, particularly their parkinsonism. Clinically, levodopa had a little effect on parkinsonism, whereas an antihistamine drug, diphenylpyraline hydrochloride (DPP) had excellent effects on all three patients throughout the long-term follow up. The mechanism of the action of DPP on parkinsonism is unclear, however, the drug seems to be a therapeutic choice for treating parkinsonism in CTX.

Topics: Adult; Brain; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Parkinsonian Disorders; Piperidines; Xanthomatosis, Cerebrotendinous

A simple, precise and accurate HPLC method was developed for the simultaneous estimation of phenyl-propanolamine HCl, guaiphenesin and diphenylpyraline HCl in syrup. The method was carried out on a Shimpak C8 column with a mobile phase consisting of acetonitrile-triethylamine (pH adjusted to 3.5 using orthophosphoric acid; 0.5%), (35:65, v/v) at a flow rate of 1.2 ml min(-1). Detection was carried out at 210 nm. Diphenhydramine was used as internal standard. The validation of the method was also carried out.

Topics: Chromatography, High Pressure Liquid; Guaifenesin; Phenylpropanolamine; Piperidines

The determination of antihistamines based on the measurement of the critical micelle concentration (c.m.c.) of mixed sodium dodecyl sulfate (SDS)-antihistamine aggregates is proposed. The dye Coomassie Brilliant Blue G (CBBG) was used as a photometric probe for the rapid determination of c.m.c.s. The micellar properties of these drugs permitted the determination of diphenhydramine, antazoline, tripelennamine, diphenylpyraline and clemizole at the micron level with detection limits ranging between 0.1 and 0.7 microns. Hence the proposed method surpassed existing alternative photometric methods used routinely in the quality control of these drugs in sensitivity and featured similar detection limits to fluorimetric methods. The relative standard deviation for 6 micron diphenhydramine was 3.7%. The method was applied to the determination of these drugs in pharmaceutical preparations (solutions, capsules, creams and pills). which were analyzed directly after dissolution of the samples in distilled water.

Topics: Antazoline; Benzimidazoles; Diphenhydramine; Histamine H1 Antagonists; Micelles; Pharmaceutical Preparations; Piperidines; Spectrophotometry; Titrimetry; Tripelennamine

A rapid, reliable and specific reversed-phase high-performance liquid chromatographic procedure is described for the determination of diphenylpyraline hydrochloride at nanogram concentrations in plasma and urine. After extraction of the drug with n-pentane-2-propanol (50:1) from alkalinized samples, the organic extract was evaporated to dryness, reconstituted with methanol and chromatographed using a 5-micron Asahipak ODP-50 C18 column with UV detection at 254 nm. The elution time for diphenylpyraline was 7.9 min. The overall recovery of diphenylpyraline from spiked plasma and urine samples at concentrations ranging from 53 to 740 ng/ml were 94.65% and 92.29%, respectively. Linearity and precision data for plasma and urine standards after extraction were acceptable. The limit of detection was 15 ng/ml for both plasma and urine samples at 0.002 AUFS.

Topics: Chromatography, High Pressure Liquid; Histamine H1 Antagonists; Humans; Piperidines; Sensitivity and Specificity; Spectrophotometry, Ultraviolet

Prostaglandin E1 (PGE1) is known to possess various actions in vivo. Of these actions, the contraction of the ileum and inflammation are undesirable side effects. We previously proposed a hypothesis concerning the receptors for human blood platelet aggregation and its inhibition, and the contraction of the ileum and uterus based on a study of structure-activity relationships. If the same principle can be applied to contraction of the ileum and inflammation induced by PGE1, compounds that suppress the side effects of PGE1 can be developed. The antihistamine diphenylpyraline and the anticholinergic atropine antagonized PGE1-induced contraction of the ileum in guinea pigs. Papaverine, which is a smooth muscle relaxant, also acted as an antagonist. Gabexate mesylate (FOY), a non-peptide proteinase inhibitor, inhibits guinea pig ileum contraction induced by PGE1, but epsilon-guanidinocaproic acid (GCA), a metabolite of FOY, does not. Increased microvascular permeability of the abdominal skin in rats induced by the local injection of PGE1 and histamine was suppressed by atropine, papaverine and diphenylpyraline. FOY, not GCA, had a weak inhibitory action. We demonstrate the possibility of suppressing the side effects of PGE1 based on the results obtained in the present and previous studies.

Topics: Alprostadil; Animals; Atropine; Capillary Permeability; Gabexate; Guanidines; Guinea Pigs; Histamine; Ileum; Inflammation; Male; Muscle Contraction; Papaverine; Piperidines; Rats

Two sibling cases of cerebrotendinous xanthomatosis with parkinsonism were reported. One was a woman of 39 years old, and another was her sister of 36 years old. In both cases, febrile convulsion appeared on 1.5 year old, and mental deterioration, ataxic -spastic gait, cataract and swelling of Achilles tendons developed in order since entrance into elementary school. Five years ago, while they were in hospital at the first time, they were diagnosed as cerebrotendinous xanthomatosis by mental disturbance, cerebellar ataxia, pyramidal tract sign, histologically xanthomatous granuloma of Achilles tendons and hypercholestanolemia and family history of autosomal recessive trait. After the second admission, parkinsonism was noticed in addition to those findings above. Parkinsonism consisted of the following: Resting tremor of parkinsonian type, mild muscle rigidity of forearm and intrinsic-plus hand were observed in the elder sister, and generalized severe rigidity and bradykinesia in the younger sister. In both cases, brain CT showed the pontocerebellar atrophy, and the bilateral low density area in corona radiata, posterior portion of internal capsule, cerebral peduncle, tegmentum of midbrain and deep matter of cerebellum. Brain MRI also showed abnormal intensity in the same regions as on the brain CT. Administration of anti-parkinsonian drugs was challenged for the parkinsonism. Oral L-dopa test (500 mg) moderately improved parkinsonism in both cases. Therapy of diphenylpyraline hydrochloride (10 mg/day) entirely inhibited parkinsonian tremor and mild rigidity in the elder sister but was less effective for severe rigidity in the younger sister than administration of L-dopa.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Achilles Tendon; Adult; Brain Diseases; Female; Humans; Magnetic Resonance Imaging; Parkinson Disease; Piperidines; Tomography, X-Ray Computed; Xanthomatosis

The effects of three commonly used H1 antihistamines on the nasal vascular and airway resistances were studied in the dog. Promethazine hydrochloride decreased nasal vascular resistance but increased nasal airway resistance in a dose-dependent manner. Diphenylpyraline hydrochloride in low doses increased nasal vascular resistance without affecting much nasal airway resistance while in high doses decreased nasal vascular resistance but increased nasal airway resistance. Chlorpheniramine maleate in low doses increased nasal vascular resistance but decreased nasal airway resistance while in high doses decreased nasal vascular resistance without affecting much nasal airway resistance. It was concluded that different H1 antihistamines might exert vasoconstrictor or vasodilatatory action on both the resistance and capacitance vessels of the nasal vascular bed depending on the type and the dose of the drug used.

Topics: Airway Resistance; Animals; Chlorpheniramine; Dogs; Dose-Response Relationship, Drug; Female; Histamine H1 Antagonists; Male; Nasal Mucosa; Piperidines; Promethazine; Vascular Resistance

A GLC method for determining theophylline, hydroxyethyltheophylline, and diphenylpyraline hydrochloride is presented. The method permits the separation and quantitative determination of the therapeutically active ingredients with a single injection in an overall time of approximately 2.5 hr.

Topics: Benzhydryl Compounds; Chromatography, Gas; Drug Combinations; Histamine H1 Antagonists; Methods; Piperidines; Solutions; Theophylline

The effect of sodium chloride on the micellar properties of the antihistamines, dephenhydramine hydrochloride, bromodiphenhydramine hydrochloride, chlorcyclizine hydrochloride and diphenylpyraline hydrochloride in aqueous solution has been investigated by light scattering and viscometric methods. The drugs behaved as typical ionic surfactants showing an increase in aggregation number and decrease in critical micelle concentration as the electrolyte concentration was increased over the range 0.05 to 0.154 mol kg-minus1. A linear relation between log critical micelle concentration and log counterion concentration was established, from which values of the degree of ionization and the free energy of micellization were calculated. The intrinsic viscosity was decreased by the addition of electrolyte and this has been attributed to a decrease in micellar hydration due to a removal of hydrogen-bonded water.

Topics: Benzhydryl Compounds; Chemical Phenomena; Chemistry; Diphenhydramine; Histamine H1 Antagonists; Mathematics; Methyl Ethers; Micelles; Piperazines; Piperidines; Sodium Chloride; Viscosity

Topics: Anti-Allergic Agents; Caffeine; Connective Tissue; Elastin; Fetus; Glycosaminoglycans; Hexosamines; Histamine H1 Antagonists; Mice; Pharmacology; Piperidines; Pregnancy; Research

Topics: Abnormalities, Drug-Induced; Anti-Allergic Agents; Caffeine; Fetal Death; Histamine H1 Antagonists; Mice; Piperidines; Pregnancy; Pregnancy, Animal; Research; Thalidomide; Theophylline; Toxicology

Topics: Anti-Allergic Agents; Histamine H1 Antagonists; Hypersensitivity; Piperidines

Topics: Anti-Allergic Agents; Histamine H1 Antagonists; Hyperthermia, Induced; Piperidines; Rhinitis, Allergic, Seasonal

Topics: Anti-Allergic Agents; Dermatology; Histamine H1 Antagonists; Medicine; Piperidines

Topics: Antifungal Agents; Fungicides, Industrial; Piperidines; Tinea; Tinea Pedis

Topics: Anti-Allergic Agents; Histamine H1 Antagonists; Hypersensitivity; Piperidines

Topics: Anti-Allergic Agents; Histamine H1 Antagonists; Humans; Piperidines

Topics: Anti-Allergic Agents; Antifungal Agents; Asthma; Conjunctivitis; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic, Seasonal

Topics: Antifungal Agents; Fungicides, Industrial; Mycoses; Piperidines

Topics: Antifungal Agents; Fungicides, Industrial; Humans; Piperidines