piperidines and Raynaud-Disease

OPC-28326 is a selective alpha-adrenergic antagonist with preferential binding to the alpha(2C)-adrenergic receptor (alpha(2C)-AR) subtype. This study observed the effect of OPC-28326 on skin temperature and digital blood flow following an acute cold challenge in patients with Raynaud's phenomenon secondary to scleroderma.. The study was designed as a single-center, double-blind, placebo-controlled, randomized, 3-period crossover study of OPC-28326 (oral doses of 10 mg or 40 mg) or placebo. The primary outcome measures were the time to recover 50% and 70% of the fall (induced by cold challenge) in baseline digital skin temperature.. Twelve of 13 enrolled patients completed the study. The mean time to achieve 50% and 70% recovery of the change in prechallenge digital skin temperature was shorter after the OPC-28326 40-mg dose than after placebo (50% recovery at 5.8 minutes versus 10.0 minutes [P = 0.02]; 70% recovery at 13.8 minutes versus 19.5 minutes [P = 0.01]). These recovery times tended to be shorter in the 10 mg OPC-28326 group as well, but the difference versus placebo was not significant (50% recovery at 9.0 minutes versus 10.0 minutes [P = 0.65]; 70% recovery at 15.3 minutes versus 19.5 minutes [P = 0.07]). Total digital blood flow tended to be lower prior to the cold challenge and after administration of 40 mg OPC-28326, as compared with that after placebo, but the difference was not significant. Symptoms that were potentially drug-related were reported more frequently with 40 mg OPC-28326 than with 10 mg OPC-28326 or with placebo, but none were serious or sustained.. OPC-28326 at doses of 10 mg and 40 mg was well tolerated during this study. The shorter time to skin temperature recovery after 40 mg OPC-28326 suggests that selective alpha(2C)-AR blockade improves digital skin perfusion during recovery from cooling in patients with Raynaud's phenomenon secondary to scleroderma.

Topics: Administration, Oral; Adolescent; Adrenergic alpha-Antagonists; Adult; Aged; Aged, 80 and over; Aniline Compounds; Cold Temperature; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fingers; Humans; Male; Middle Aged; Piperidines; Raynaud Disease; Regional Blood Flow; Scleroderma, Systemic; Skin Temperature; Vasodilation

In a double blind placebo crossover study, intravenous ketanserin, an antagonist of S2-serotonergic receptors, did not improve plethysmographically monitored digital blood flow during controlled cold challenge in 4 women with carefully defined primary Raynaud's phenomenon. However, ketanserin, if administered at the time of cold induced vasoconstriction, caused prompt vasodilation. These results suggest that serotonin is a contributory element in the maintenance of cold induced vasospasm but that other factors, presumedly adrenergic, initiate the vasoconstrictive response.

Topics: Adult; Cold Temperature; Female; Humans; Ketanserin; Piperidines; Raynaud Disease; Receptors, Adrenergic; Receptors, Serotonin; Vasoconstriction

Ketanserin, 40 mg b.i.d., or matching placebo were administered for 8 weeks each in a randomised double-blind crossover design to 23 patients with Raynaud's phenomenon. Ketanserin had no effect on Doppler arterial patency or blood flow at rest, 37 degrees C, 15 degrees C, or during recovery after cold challenge. Red cell deformability index and whole blood viscosity were not significantly affected by ketanserin treatment. In vivo bleeding time was prolonged on ketanserin (p less than 0.05) but beta-thromboglobulin and platelet factor 4 were unaffected. There was a nonsignificant decrease in platelet aggregation response to serotonin but no change at all with other aggregating agents on treatment with ketanserin.

Topics: Adult; Aged; Blood Platelets; Blood Viscosity; Female; Fingers; Humans; Ketanserin; Male; Middle Aged; Piperidines; Raynaud Disease; Regional Blood Flow; Rheology; Serotonin Antagonists

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Ketanserin; Male; Middle Aged; Piperidines; Raynaud Disease; Serotonin Antagonists

In 41 patients with primary Raynaud's phenomenon (PRP) the effectiveness of the serotonin receptor blocker Ketanserin has been studied in a double-blind cross-over investigation and during an additional long-term open study. Objective assessments of the severity of PRP in the patients were obtained by measuring Digital Skin Temperature (DST), Digital systolic Blood Pressure (DBP) and Doppler Spectral Analysis (DOSA) of the radial and ulnar artery. All measurements were performed both before and after cold provocation. Thirty one (78%) of the patients clinically improved on Ketanserin, while only 1 patient (2.3%) improved on placebo. DST significantly increases on Ketanserin treatment. On Ketanserin treatment DBP measurements show a significant increase in the digit to brachial systolic blood pressure index (DBI) after cold provocation. DOSA showed a significant decrease of the downslope of the spectra of both radial and ulnar artery on treatment. This downslope is indicative for peripheral resistance. Neither blood chemistry nor systemic blood pressure showed any change during Ketanserin treatment. The results of the study suggest that orally administered Ketanserin can be an effective and well tolerated treatment for minimizing subjective complaints in PRP patients. Ketanserin results in an increased DST and DBP combined with a decreased peripheral resistance as measured on the radial and ulnar artery. After treatment, Ketanserin does not show any side effects.

Topics: Adolescent; Adult; Aged; Blood Flow Velocity; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Ketanserin; Male; Middle Aged; Piperidines; Random Allocation; Raynaud Disease; Skin Temperature; Vascular Resistance

Ketanserin, a selective antagonist of the 5-HT2 receptor, was evaluated in a 4-week open pilot trial of 30 patients with Raynaud's phenomenon. Moderate or marked relief was reported in 15 of 18 (83%) patients with systemic sclerosis, whereas only 4 of 12 (33%) patients with Raynaud's phenomenon of other etiology received such benefit (P less than 0.01). These subjective ratings were supported by the results of serial digital strain gauge plethysmography during controlled cold challenge. Additional clinical findings suggested that ketanserin therapy facilitated the healing of ischemic digital ulcerations and reduced hand edema in patients with systemic sclerosis. These findings lend support to the hypothesis that serotonin is an important element in the pathogenesis of systemic sclerosis.

Topics: Adult; Aged; Clinical Trials as Topic; Female; Fingers; Humans; Ketanserin; Male; Middle Aged; Pilot Projects; Piperidines; Plethysmography; Raynaud Disease; Receptors, Serotonin; Regional Blood Flow; Scleroderma, Systemic; Serotonin Antagonists

The serotonin receptor blocker ketanserin was given orally in a double blind crossover study to 10 patients with connective tissue disorders and Raynaud's phenomenon. Eight of the 10 patients improved clinically on ketanserin and none on placebo. Digital blood flow was assessed with laser Doppler flowmetry (LDF), photoplethysmography, and skin temperature measurements. Laser Doppler flowmetry was the most useful method, showing a significant reduction in recovery time after a standard cold provocation. Although the resting flow was not significantly improved, digital ulcers healed in four out of five patients, providing evidence of increased nutritive flow. The results of this study suggest that orally administered ketanserin may be an effective and well tolerated treatment for Raynaud's phenomenon associated with connective tissue disorders, especially scleroderma.

Topics: Adult; Clinical Trials as Topic; Connective Tissue Diseases; Double-Blind Method; Female; Fingers; Humans; Ketanserin; Microcirculation; Middle Aged; Piperidines; Raynaud Disease; Scleroderma, Systemic; Serotonin Antagonists; Ultrasonography

The selective 5-hydroxytryptamine2-(5-HT2)-receptor-blocking agent ketanserin was given in a dose of 10 mg intravenously to nine patients with Raynaud's phenomenon. The effect on blood flow was assessed by photopletysmography and measurments of skin temperature. Digital blood flow and skin temperature increased significantly after ketanserin injection, whereas the placebo (saline 9 g/l) had no such effect. This study suggests that ketanserin may be useful in the treatment of Raynaud's phenomenon.

Topics: Adult; Aged; Female; Fingers; Humans; Ketanserin; Male; Middle Aged; Piperidines; Raynaud Disease; Regional Blood Flow; Serotonin Antagonists; Skin Temperature

Topics: Anesthesia, General; Bundle-Branch Block; Dermatomyositis; Dyslipidemias; Epoprostenol; Female; Fentanyl; Furosemide; Humans; Hypertension; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Mediastinal Diseases; Mediastinoscopy; Methyl Ethers; Middle Aged; Oxygen Inhalation Therapy; Piperidines; Preoperative Care; Raynaud Disease; Remifentanil; Sevoflurane; Spironolactone

The effect of ketanserin, a serotonin 5-HT2 receptor inhibitor, on the cold-provoked vasospasm in arsenic workers was examined by measuring the finger systolic pressure (FSP). After injection of 10 mg ketanserin the skin temperature and the FSP of the cooled finger increased significantly. Prolonged oral treatment with ketanserin, 2 X 40 mg per day, did not significantly influence the skin temperature or FSP during local cooling in arsenic workers or patients with primary or vibration-induced Raynaud's phenomenon. The effect of ketanserin intravenously indicates that serotonin is involved in the mechanism behind vasospasm of arsenic workers in the same way as it is known to be in patients with primary and vibration-induced Raynaud's phenomenon.

Topics: Administration, Oral; Adult; Arsenic Poisoning; Blood Pressure; Double-Blind Method; Hand; Humans; Injections, Intravenous; Ketanserin; Male; Middle Aged; Piperidines; Random Allocation; Raynaud Disease; Regional Blood Flow; Skin Temperature; Vibration

We report five children who presented with Raynaud's disease in whom we could find no clinical, haematological, or immunological evidence of a collagen disorder. Oral phenoxybenzamine proved useful for maintenance treatment in most, with infusions of prostacyclin, nitroprusside, and ketanserin during acute attacks.

Topics: Antihypertensive Agents; Child; Dinoprostone; Epoprostenol; Female; Humans; Ketanserin; Male; Nifedipine; Nitroprusside; Phenoxybenzamine; Piperidines; Prostaglandins E, Synthetic; Raynaud Disease

Topics: Arteriosclerosis Obliterans; Humans; Piperidines; Plethysmography; Propiophenones; Raynaud Disease; Theophylline; Xanthinol Niacinate

Topics: Adrenergic alpha-Agonists; Adult; Aged; Arteriosclerosis; Benzamides; Blood Pressure; Female; Fingers; Heart Rate; Humans; Hypotension; Indoles; Injections, Intravenous; Intermittent Claudication; Male; Middle Aged; Piperidines; Pulse; Radioisotopes; Raynaud Disease; Regional Blood Flow; Skin; Time Factors; Toes; Xenon