piperidines and Hyperemia

To address the current trends of therapeutic mechanisms for treatment of allergic conjunctivitis (AC), based on topical antihistamines and mast cell stabilizers (MCS).. The antihistamine drug alcaftadine has H4 receptor inverse agonism, anti-inflammatory and MCS activities. The antihistamines levocabastine and azelastine are more effective than placebo in treatment of AC symptoms in randomized controlled trials (RCTs). The topical dual-action antihistamines/MCS olopatadine, azelastine, ketotifen, and epinastine are commonly used in Europe and in the United States for mild subtypes of AC. For the main symptoms of AC, ocular itch and conjunctival hyperemia, epinastine 0.05% was superior to placebo, but equal or more effective than olopatadine 0.1%, while the later was more effective than ketotifen. High concentration olopatadine 0.77% had longer duration of action, better efficacy on ocular itch, and a similar safety profile to low-concentration olopatadine 0.2%. The new formulas of topical dual-action agents present longer duration of action, leading to a decreased frequency of use.. The topical dual-action agents are the most effective agents treating signs and symptoms of mild forms of AC. There is superiority to the high-concentration olopatadine drug over other agents on ocular itch, with prolonged effect when used once-daily.

Topics: Administration, Ophthalmic; Anti-Allergic Agents; Benzazepines; Conjunctivitis, Allergic; Cromolyn Sodium; Dibenzazepines; Histamine Antagonists; Humans; Hyperemia; Imidazoles; Ketotifen; Nedocromil; Olopatadine Hydrochloride; Phthalazines; Piperidines; Pruritus; Pyridines; Pyrimidinones

This clinical trial evaluated the safety and effectiveness of bepotastine besilate ophthalmic solutions 1.0% and 1.5% compared with placebo for the treatment of ocular itching and conjunctival hyperemia (redness) using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis when dosed 16 h before a CAC test.. Subjects with a history of allergic conjunctivitis were assigned to receive placebo or bepotastine besilate ophthalmic solution 1.0% or 1.5% in a single-center, randomized, placebo-controlled clinical trial. Eligible subjects (n=107) aged 10 years and older with a history of allergic conjunctivitis who had a reproducible positive reaction to a CAC were enrolled and dosed with test agent. The primary trial objectives included assessment of ocular itching and conjunctival redness at 16 h after instillation of test agent. Reductions in several CAC-induced secondary symptoms and signs of allergic conjunctivitis were also evaluated for tearing, ciliary and episcleral redness, eyelid swelling, chemosis, and mucous discharge.. Bepotastine besilate ophthalmic solution 1.5% demonstrated clinical effectiveness and statistical significance in comparison to placebo for the reduction in CAC-induced ocular itching 16 h after drug administration. Bepotastine besilate ophthalmic solution 1.0% also achieved statistical significance in comparison to placebo for reducing ocular itching at all time points 16 h after dosing. Statistically significant reduction (P≤0.05) was additionally seen in this CAC test for the secondary ocular efficacy variable of allergen-induced tearing for bepotastine besilate ophthalmic solution 1.5%. No clinical benefit was seen for reducing the coprimary efficacy variable of conjunctival redness with the CAC model of allergic conjunctivitis.. Bepotastine besilate ophthalmic solution 1.5% produced predefined clinically meaningful reduction in CAC-induced ocular itching and tearing in a single-site trial and was more effective than bepotastine besilate ophthalmic solution 1.0% and placebo for reducing ocular itching in a CAC test 16 h after dosing.

Topics: Adolescent; Adult; Aged; Anti-Allergic Agents; Child; Conjunctiva; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hyperemia; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Prospective Studies; Pruritus; Pyridines; Time Factors; Young Adult

To evaluate the effectiveness of bepotastine besilate ophthalmic solutions 1.0% and 1.5% compared with placebo at reducing ocular itching and conjunctival hyperemia in the conjunctival allergen challenge (CAC) model of allergic conjunctivitis.. Prospective, double-masked, randomized, placebo-controlled, phase 3 CAC clinical trial.. This multicenter trial enrolled 130 subjects with a clinical history of allergic conjunctivitis who were randomized to bepotastine besilate ophthalmic solution 1.0%, 1.5%, or 0.0% (placebo). One drop of test agent was instilled bilaterally before a CAC test evaluating responses at 15 minutes, 8 hours, or 16 hours after test agent instillation. Primary efficacy outcomes were unit improvements relative to placebo in mean scores for ocular itching and conjunctival hyperemia, each graded on 0- to 4-unit scales.. Reductions of 1.2 units or more in mean ocular itching scores at all time points for both bepotastine besilate ophthalmic solutions 1.0% and 1.5% were observed at onset of action and 8-hour duration-of-action CAC tests (P < .0001). Statistically significant reductions in conjunctival hyperemia (P < or = .0125) were observed for bepotastine besilate ophthalmic formulations only at the onset of action CAC test.. Bepotastine besilate ophthalmic solutions 1.0% and 1.5% both substantially decreased CAC-induced ocular itching for at least 8 hours after dosing. Reductions in conjunctival hyperemia after a CAC, although statistically significant for bepotastine besilate ophthalmic solutions 1.0% and 1.5% compared with placebo when assessed at 15 minutes after dosing, were modest.

Topics: Adolescent; Adult; Anti-Allergic Agents; Child; Conjunctiva; Conjunctivitis, Allergic; Double-Blind Method; Female; Humans; Hyperemia; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Prospective Studies; Pyridines; Treatment Outcome; Visual Acuity

Approximately 16.2% of the Japanese population suffer from cedar pollinosis, with various manifestations such as ophthalmic, laryngo-pharyngeal and skin symptoms in addition to nasal symptoms. Thus, the annual pollen season is an agonizing period for patients. No study has reported symptoms and their clinical courses after conjunctival provocation with purified cedar pollen allergen Cry j1 as well as suppression of these allergen-induced ocular symptoms by antihistamine eye drops.. Nine patients with Japanese cedar pollinosis who had no nasal or ocular symptoms were included in the present study, after obtaining informed consent in writing. 1) Purified cedar pollen allergen Cry j1 was instilled in the left eye and phosphate-buffered saline (PBS) in the right eye as a control. 2) Levocabastine hydrochloride ophthalmic suspension and ketotifen fumarate ophthalmic solution were respectively instilled in the left and right eyes, which were then challenged with the allergen. Ocular symptoms after provocation with the allergen were recorded through the clinical course.. Pollen allergen-induced ocular symptoms were itching and hyperemia of the palpebral conjunctiva, and itching lasted for more than 5 hours. Moreover, preadministration of antihistamine eye drops suppressed the increases in the ocular symptom scores, eliminating itching within 1 hour. Allergen provoked not only ocular symptoms but also nasal symptoms in 77.8% of patients.. Preadministration of antihistamine eye drops suppressed the symptoms induced by the allergen, which suggests that this is an effective early therapy for Japanese cedar pollinosis, if it is started before the pollen season. However, self-protection by patients using a mask may not be effective enough to suppress nasal symptoms during the pollen season, requiring them to additionally wear glasses to avoid exposure to the allergen.

Topics: Adult; Allergens; Antigens, Plant; Conjunctivitis, Allergic; Cryptomeria; Dose-Response Relationship, Immunologic; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Hyperemia; Japan; Ketotifen; Ophthalmic Solutions; Piperidines; Plant Proteins; Pollen; Premedication; Pruritus; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Treatment Outcome

Topics: Aged; Ancrod; Arterial Occlusive Diseases; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Humans; Hyperemia; Intermittent Claudication; Lactates; Middle Aged; Physical Exertion; Piperidines; Pyruvates

Transient receptor potential vanilloid 4 (TRPV4) channels exist on vascular endothelial cells and eccrine sweat gland secretory cells in human skin. Here, we assessed whether TRPV4 channels contribute to cutaneous vasodilation and sweating during whole body passive heat stress (

Topics: Adult; Female; Humans; Hyperemia; Hyperthermia; Leucine; Male; Membrane Transport Modulators; Microdialysis; Morpholines; Piperidines; Pyrroles; Quinolines; Regional Blood Flow; Skin; Sulfonamides; Sweating; Time Factors; TRPV Cation Channels; Vasodilation; Young Adult

The effects of different body positions on the middle ear were reported in several studies, but there are no data about the effects on patients under general anesthesia. The aim of this study is to determine the effect of prone position on middle ear pressure (MEP) during general anesthesia without using nitrous oxide.. Twenty patients under general anesthesia during prone position were included in the study. The performed anesthesia method was the same for all patients. Remifentanil was used for analgesia instead of nitrous oxide. MEPs were measured 5 times with a middle ear analyzer: before induction (BI), after intubation (AI), after turned to the prone position (PP1), at the end of the prone position (PP2), and after returned to the supine position (SP). Duration of prone position was also recorded.. Of the 20 patients were 11 women and 9 men with a 49 ± 13 mean age. BI-AI, AI-PP1, PP1-PP2, and PP2-SP comparisons of both MEPs were statistically significant (P < 0.0001). Right mean MEPs were BI, -1 ± 23 daPa; AI, 41 ± 51 daPa; PP1, 124 ± 76 daPa; PP2, 152 ± 59 daPa; and SP, 63 ± 29 daPa; whereas left mean MEPs were BI, -24 ± 55 daPa; AI, 28 ± 34 daPa; PP1, 132 ± 67 daPa; PP2, 162 ± 48 daPa; and SP, 70 ± 89 daPa. Significant increases were detected at the start and continuation of the prone position. The mean duration of prone position was 98 ± 51 per minute.. The significant MEP increases during the prone position under general anesthesia depend on a number of reasons. Among them are inhaler agents, pressure changes in mucosal blood vessels due to venous congestion, and the mastoid bone volume. Further researches are required to determine and explain the mechanisms of increase in MEP during prone position.

Topics: Adult; Anesthesia, General; Anesthetics, Intravenous; Ear, Middle; Female; Follow-Up Studies; Humans; Hyperemia; Male; Mastoid; Middle Aged; Mucous Membrane; Piperidines; Pressure; Prone Position; Remifentanil; Supine Position; Time Factors

In vitro studies demonstrate that cannabinoid CB(1) receptors subserve activity-dependent suppression of inhibition in the neocortex. To examine this mechanism in vivo, we assessed the effects of local changes in CB(1) receptor activity on somatosensory cortex neuronal activation by whisker movement in rats.. Laser Doppler flowmetry and c-Fos immunohistochemistry were used to measure changes in local blood flow and neuronal activation, respectively. All drugs were applied directly to the cranium above the whisker barrel fields of the primary somatosensory cortex.. The CB(1) receptor agonist WIN55212-2 potentiated the hyperaemia induced by whisker movement and this potentiation was occluded by bicuculline. The CB(1) receptor antagonists, rimonabant and AM251, inhibited hyperaemic responses to whisker movement; indicating that activation of endogenous CB(1) receptors increased during whisker movement. Whisker movement-induced expression of c-Fos protein in neurons of the whisker barrel cortex was inhibited by rimonabant. Movement of the whiskers increased the 2-arachidonoylglycerol content in the contralateral, compared to the ipsilateral, sensory cortex.. These results support the hypothesis that endocannabinoid signalling is recruited during physiologically relevant activation of the sensory cortex. These data support the hypothesis that the primary effect of CB(1) receptor activation within the activated whisker barrel cortex is to inhibit GABA release, resulting in disinhibition of neuronal activation. These studies provide physiological data involving endocannabinoid signalling in activity-dependent regulation of neuronal activation and provide a mechanistic basis for the effects of cannabis use on sensory processing in humans.

Topics: Animals; Arachidonic Acids; Benzoxazines; Bicuculline; Cannabinoid Receptor Modulators; Endocannabinoids; Functional Laterality; Glycerides; Hyperemia; Male; Morpholines; Naphthalenes; Piperidines; Proto-Oncogene Proteins c-fos; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Rimonabant; Somatosensory Cortex; Vibrissae

Hyperdynamic circulation and mesenteric hyperaemia are found in cirrhosis. To delineate the role of endocannabinoids in these changes, we examined the cardiovascular effects of anandamide, AM251 (CB(1) antagonist), AM630 (CB(2) antagonist) and capsazepine (VR1 antagonist), in a rat model of cirrhosis.. Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, diameters of mesenteric arteriole and venule (intravital microscopy), arterial pressure, cardiac output, systemic vascular resistance and superior mesenteric artery (SMA) flow were measured after anandamide, AM251 (with or without anandamide), AM630 and capsazepine administration. CB(1), CB(2) and VR1 receptor expression in SMA was assessed by western blot and RT-PCR.. Anandamide increased mesenteric vessel diameter and flow, and cardiac output in cirrhotic rats, but did not affect controls. Anandamide induced a triphasic arterial pressure response in controls, but this pattern differed markedly in cirrhotic rats. Pre-administration of AM251 blocked the effects of anandamide. AM251 (without anandamide) increased arterial pressure and systemic vascular resistance, constricted mesenteric arterioles, decreased SMA flow and changed cardiac output in a time-dependent fashion in cirrhotic rats. Capsazepine decreased cardiac output and mesenteric arteriolar diameter and flow, and increased systemic vascular resistance in cirrhotic rats, but lacked effect in controls. Expression of CB(1) and VR1 receptor proteins were increased in cirrhotic rats. AM630 did not affect any cardiovascular parameter in either group.. These data suggest that endocannabinoids contribute to hyperdynamic circulation and mesenteric hyperaemia in cirrhosis, via CB(1)- and VR1-mediated mechanisms.

Topics: Animals; Arachidonic Acids; Bile Ducts; Blood Flow Velocity; Blood Pressure; Blotting, Western; Capsaicin; Cardiac Output; Disease Models, Animal; Endocannabinoids; Hyperemia; Indoles; Liver Circulation; Liver Cirrhosis, Biliary; Male; Mesenteric Artery, Superior; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Splanchnic Circulation; Time Factors; TRPV Cation Channels; Vascular Resistance; Vasodilation; Vasodilator Agents

Since exogenously applied tachykinins (substance P and neurokinin A) prevent the neurogenic hyperaemia which is elicited by acid back-diffusion in the rat stomach, we investigated whether endogenous tachykinins would act in a similar manner. Acid back-diffusion, induced by perfusing the stomach with 15% ethanol in the presence of 0.05 M HCI, increased gastric mucosal blood flow (GMBF) by 60-100% as determined by hydrogen clearance in urethane-anaesthetized rats. This response remained unchanged after pretreatment with the tachykinin NK1 receptor antagonist SR 140,333 (300 nmol/kg) but tended to be enhanced by the NK2 receptor antagonist MEN 10,627 (200 nmol/kg). When given during ongoing acid back-diffusion, MEN 10,627 significantly enhanced the acid-evoked vasodilatation as compared with vehicle or SR 140,333. We conclude that endogenously released tachykinins, acting via NK2 receptors, limit the gastric hyperaemic response to acid.

Topics: Animals; Blood Pressure; Female; Gastric Acid; Heart Rate; Hyperemia; Ligands; Peptides, Cyclic; Piperidines; Quinuclidines; Rats; Rats, Sprague-Dawley; Receptors, Neurokinin-1; Receptors, Neurokinin-2; Regional Blood Flow; Stomach; Vasodilation

A new technique consisting of continuous intraarterial infusion of the ultra-short-lived 81mKr for the study of blood flow in patients with severe peripheral vascular disease is described. With the gamma camera high resolution images and typical time activity curves, reflecting local regional blood flow in the feet, could be obtained under resting conditions during reactive hyperemia and administration of vasodilating drugs. Preliminary promising results of Ketanserin, a new selective serotonin antagonist, in patients with impending gangrene and ulcerations are discussed.

Topics: Animals; Arteriosclerosis Obliterans; Cats; Diabetic Angiopathies; Female; Humans; Hyperemia; Ketanserin; Krypton; Leg; Male; Piperidines; Radioisotopes; Radionuclide Imaging; Regional Blood Flow; Serotonin; Serotonin Antagonists; Thromboangiitis Obliterans; Vascular Diseases

A number of derivatives of piperidine-2,4,6-trione and oxazine-2,4-dione with cyclohexyl and allyl substituents at their ring were evaluated pharmacologically. Piperidine-2,4,6-trione compounds, regardless of type of substituent, were readily absorbed from the site of their introduction and displayed similar biological activity. Introduction of the N-cyclohexylcarboxamide substituent diminished general toxicity of the derivative and increased anti-inflammatory activity in all tests. The oxazine-4,6-dione derivatives were poorly absorbed. The bis-(1-cyclohexyl-5,5-diallyl-piperidine-2,4,6-trione) derivative, product of condensation of two molecules of a simpler compound, was very well absorbed, strongly toxic, and showed distinct anti-inflammatory activity. Limited correlation between chemical structure and biological activity was noted, supporting the concept that introduction of cyclohexyl and allyl radicals imparts anti-inflammatory and immunosuppressive activity to derivatives of this type.

Topics: Animals; Anti-Inflammatory Agents; Antibody-Producing Cells; Chemical Phenomena; Chemistry; Drug Evaluation, Preclinical; Guinea Pigs; Hyperemia; Immunosuppressive Agents; Lethal Dose 50; Mice; Piperidines; Piperidones; Rats; Tuberculin Test

Topics: Anticonvulsants; Arteriosclerosis; Blood Flow Velocity; Humans; Hyperemia; Leg; Muscles; Piperidines; Propiophenones; Regional Blood Flow; Thigh; Time Factors