Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 Atenolol 0.2 mg/kg i.v., propranolol 0.2 mg/kg i.v. or placebo were given in a double-blind crossover study to six healthy male subjects, and the effects of a subsequent infusion of epoprostenol (prostacyclin, PGI2) 0-6 ng kg-1 min-1 monitored. 2 PGI2 caused a tachycardia, a fall in diastolic blood pressure, a rise in pulse pressure, reduction in pre-ejection period (PEP) and rise in left ventricular ejection time index (LVETI), headache and facial flushing at doses of PGI2 greater than 2 ng kg-1 min-1,, (P less than 0.05). 3 Beta-adrenoceptor blockade did not prevent the tachycardia in response to PGI2, and did not interact with any of the other dynamic effects of PGI2. 4 In vitro, PGI2 at 1 and 2 ng/ml inhibited platelet aggregation to ADP (P less than 0.01), although no significant effect on platelet aggregation was seen in the in vivo study. Atenolol and propranolol at a final concentration of 1 microgram/ml did not affect this in vitro study. Atenolol and propranolol at a final concentration of 1 microgram/ml did not affect in vitro effect of PGI2 on platelet aggregation. 5 Pretreatment with atropine 0.04 mg/kg i.v. in three subjects did not attenuate the tachycardia caused by PGI2 infusion, even though the baseline heart rate was increased. 6 Adverse effects to PGI2 infusion included sudden bradycardia, pallor and sweating, suggesting that the Bezold-Jarisch reflex seen in animals in response to PGI2 may also occur in humans. 7 Neither increased sympathetic drive nor vagal withdrawal are likely causes of the tachycardia following PGI2 infusion.
 ...
PMID:The cardiovascular and platelet effects of epoprostenol (prostacyclin, PGI2) are unaffected by beta-adrenoceptor blockade in man. 612 95

Clinical tolerance, inhibition of platelet aggregation and intracellular platelet adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were evaluated in normal volunteers given i.v. infusions of prostacyclin sodium at rates up to 15 ng/kg/min. Short-term infusions (30 and 60 minutes) were tolerated at rates up to 10.0 ng/kg/min; higher rates produced headaches, anxiety, nausea and vomiting. Six-hour and 24-hour infusions were tolerated at rates up to only 4.0 ng/kg/min. Twenty-four hour infusions at 4 ng/kg/min produced a consistent 4-7 microM shift to the right in the platelet ADP dose-response curve; this platelet inhibitory activity did not diminish during the infusion. Prostacyclin sodium infusion elevated intracellular cyclic AMP levels, the increases corresponding to the onset of measurable inhibition of ADP-induced aggregation, although the magnitude of the increase did not necessarily reflect the degree of inhibition. Increased template bleeding times were seen with a greater than 10-microM shift in the ADP dose-response curve. We conclude that although prostacyclin sodium has a narrow safety margin, the drug does produce platelet inhibition at infusion rates generally tolerated by healthy volunteers.
 ...
PMID:Intravenous infusion of prostacyclin sodium in man: clinical effects and influence on platelet adenosine diphosphate sensitivity and adenosine 3':5'-cyclic monophosphate levels. 626 15

Intravenous and oral administration of a chemically stable carboprostacyclin analogue, 15-cyclopentyl-omega-pentanor-5(E)-carbacyclin (ONO 41483), resulted in ex-vivo inhibition of ADP-induced platelet aggregation in man. The maximum tolerated intravenous dose was 2.5 ng/kg/min for 1 hour and this produced a mean of 27.1% inhibition in 3 volunteers. For oral administration the tolerated single dose was 200 microgram. At this dose, there was 56.3% inhibition of aggregation (mean of 3 results). High oral (400 microgram) and intravenous doses (5 and 10 ng/kg/min for 1 hour) of ONO 41483, which caused marked inhibition of aggregation (ranging 39-100%), was accompanied by flushing of face and extremities, headache and phlebitis. However, none of the doses tested produced significant changes in arterial blood pressure or heart rate.
 ...
PMID:Inhibition of platelet aggregation with intravenous and oral administration of a carboprostacyclin analogue, 15-cyclopentyl-omega-pentanor-5(E)-carbacyclin (ONO 41483) in man. 633 31

Epoprostenol (prostacyclin, PGI2) was given intravenously to seven healthy volunteers in a dose of 4 ng kg-1 min-1 over a 30 min period. Diastolic blood pressure fell but there was no change in cardiac output. The mean PGI2 concentration at the end of the infusion was 0.43 ng/ml (1.1 nM) and a significant inhibition of ADP-induced platelet aggregation occurred. Although obvious facial flushing occurred in all subjects and some subjects complained of headache, cerebral blood flow tended to fall. The results do not support the hypothesis that PGI2 acts as a physiological vasodilator involved in the homeostasis of normal cerebral blood flow.
 ...
PMID:The effect of intravenous epoprostenol (prostacyclin, PGI2) on cerebral blood flow and cardiac output in man. 636 96

In a single-blind trial 25 patients with progressive scleroderma and Raynaud's phenomenon intravenous infusions of iloprost, a prostacyclin derivative (carbaprostacyclin), were given daily for five hours during a six-day hospital stay, after a comparable initial single placebo infusion. Duration, frequency and intensity of Raynaud symptoms improved in more than 75% of the patients. This improvement was objectified by telethermometry which demonstrated acral hyperthermia and significantly briefer rewarming after standardized cooling of the hands. In addition, there was more rapid healing of ulcerations and necroses of the digital pulp. A significant inhibition of ADP- and collagen-dependent platelet aggregation was demonstrated during the iloprost infusion. Side effects, such as headache, nausea and tiredness occurred only transitorily during the infusion, were individually highly variable, and then only at higher concentrations. A dosage of 2 ng/kg X min was tolerated by all patients.
 ...
PMID:[Treatment of Raynaud's phenomenon in scleroderma with a new stable prostacyclin derivative]. 638 60

Following an open pilot study, BW 245C , a hydantoin prostaglandin analogue, was given by mouth in an aqueous solution to six healthy volunteers. The subjects received BW 245C 50 and 150 micrograms and placebo on separate occasions according to a double blind randomised design. Heart rate, blood pressure and, using visual analogue scales, facial flushing, abdominal discomfort and headache, were measured before dosing, at 15 minute intervals after dosing for 2 hours and at 30 minute intervals for a further 2 hours. Platelet aggregation responses to ADP and to collagen were measured before dosing and at 15 minutes, 45 minutes, 2 hours and 4 hours after dosing. Cutaneous bleeding time was measured before and 45 minutes after dosing. 150 micrograms BW 245C produced significant (p less than 0.05) facial flushing over the period from 15 to 120 minutes after dosing. Heart rate increased slightly but significantly (p less than 0.05) in response to both doses of 245C only at 75 minutes after dosing. Systolic and diastolic blood pressures were unchanged by either dose of BW 245C . Platelet aggregation responses to ADP were significantly (p less than 0.05) inhibited only at 120 minutes after 150 micrograms BW 245C . Aggregation responses to collagen were significantly (p less than 0.05) inhibited 45 and 120 minutes after 150 micrograms BW 245C and also at 120 minutes after 50 micrograms BW 245C . Bleeding time was unchanged in response to either dose of BW 245C . There was no change in headache or abdominal discomfort scores following either dose of BW 245C . Nausea was reported after 7 out of 12 administrations of BW245C but not after placebo. Nasal congestion was experienced by two subjects receiving 150 micrograms BW 245C and muscle tension and stiffness, especially of the jaw muscles, was also reported following administration of BW 245C but not of placebo. BW 245C is active when given by mouth and has similar pharmacodynamic effects to prostacyclin in man.
 ...
PMID:Effects of single oral dose administration of a hydantoin prostaglandin analogue BW 245C in man. 672 64

Intravenous infusion of carboprostacyclin, a chemically stable analogue of prostacyclin (PGI2) resulted in ex-vivo inhibition of ADP-induced platelet aggregation at doses that did not produce significant changes in blood pressure or heart rate. Oral administration of relatively large doses of this compound also inhibited ex-vivo ADP-induced platelet aggregation but this was accompanied by headache, facial flush, tachycardia and changes in blood pressure.
 ...
PMID:Inhibition of platelet aggregation with intravenous and oral administration of carboprostacyclin in man. 702 10

Beraprost sodium (BPS) is an orally stable analogue of prostacyclin that inhibits adenylate-cyclase-dependent platelet aggregation and is proposed for treatment of chronic arterial occlusion. To determine the duration and intensity of platelet antiaggregation with BPS, 12 healthy, nonsmoking, male white volunteers participated in a double-blind, dose-escalating design with randomized placebo, placebo-controlled, cross-over study. After overnight fasting, single (20, 40, 60 micrograms and placebo) and repeated [20, 40, 60 micrograms and placebo) and repeated [20, 40, 60 micrograms and placebo three times daily (t.i.d.) for 3 days] oral doses of BPS were administered. Mean percentage of inhibition of ADP-induced aggregation normalized to placebo was measured for 8 h after drug administration and related to plasma concentrations (Cp) of the active enantiomer (APS 314d). BPS 40 and 60 micrograms decreased platelet aggregation 1 h after single doses, and 0.5 h and 1 h after repeated doses. BPS 20 micrograms had no significant effect. APS 314d pharmacokinetics was linear, and its terminal half-life (t 1/2) ranged from 0.50 +/- 0.21 to 0.91 +/- 0.27 h (mean +/- SD) independently of BPS dose. Antiaggregating effects were poorly related to Cp of APS 314d (r2 < or = 0.2). Some subjects complained of moderate postdrug absorption headaches (7 of 12 after single and 8 of 12 after repeated doses) and flushes (6 of 12 and 7 of 12, respectively). These data indicate that orally active prostacyclin BPS (40 or 60 micrograms) exerts its maximal antiaggregating effects between 0.5 and 1 h.
 ...
PMID:Pharmacokinetics and platelet antiaggregating effects of beraprost, an oral stable prostacyclin analogue, in healthy volunteers. 750 23

Clinical efficacy of tiklid in a dose 500 mg/day and its action on platelet vascular hemostasis were evaluated in 24 patients with cerebrovascular diseases. A 15-day tiklid course promoted a regress in some subjective symptoms (headache, vertigo, walking instability, photopsias, etc.), the objective neurological status being unchanged. Tiklid had a positive influence on some rheological parameters and platelet vascular hemostasis. ADP-induced platelet aggregation, blood fibrinogen levels got reduced. The platelets sensitivity to antiaggregation agent PgI2 in vitro arose. Antiaggregation potential of the vascular wall returned to normal in 33% of patients with initially low or inverse response.
 ...
PMID:[Clinical and blood rheologic effects of ticlid in patients with cerebrovascular diseases]. 830 98

1. m-Chlorophenylpiperazine (m-CPP), a 5-HT1c-receptor agonist, induces migraine-like headaches when taken orally by migraine sufferers. The present study was undertaken to see what effects m-CPP had on 5-HT function in platelets. 2. Platelets from healthy male volunteers were loaded with [3H]-5-HT and continuously perfused in vitro with carboxygenated Krebs solution at 37 degrees C. After 30 min washout the effects of m-CPP, thrombin, 5-HT and ADP on the efflux of [3H]-5-HT were recorded. 3. m-CPP (0.5-500 microM) did not evoke an increase in the efflux of [3H]-5-HT over that occurring spontaneously whereas thrombin, unlabelled 5-HT and ADP did. The effects of 5-HT were potentiated by ADP. The results were identical whether or not the 5-HT reuptake blocker paroxetine (1 microM) was present. 4. m-CPP inhibited the increase in the efflux of [3H]-5-HT evoked by different concentrations of unlabelled 5-HT in the presence of ADP (2.5 microM) and displaced the 5-HT log concentration response curve to the right. A similar result was obtained with the 5-HT2-receptor antagonist ketanserin. 5. We conclude that m-CPP is a 5-HT2-receptor antagonist on human platelets, which is unlikely to account for its headache-inducing property, as many drugs effective in migraine prophylaxis have this action.
 ...
PMID:The effects of 5-HT and m-chlorophenylpiperazine (m-CPP) on the efflux of [3H]-5-HT from human perfused platelets. 851 59


<< Previous 1 2 3 4 Next >>