Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Dihydroergotamine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1995

Efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the treatment of acute migraine. Dihydroergotamine Nasal Spray Multicenter Investigators.

Recently, a new nasal spray formulation of dihydroergotamine was developed which facilitates at-home treatment of migraine. We studied the efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the acute treatment of classic and common migraine in two, identical, double-blind, randomized, placebo-controlled trials. Of the 229 patients enrolled, 206 (102 dihydroergotamine nasal spray, 104 placebo) were included in the intent-to-treat analyses; 182 treated two headaches and 24 treated one headache. Based on both the patients' and physicians' ratings, dihydroergotamine nasal spray was significantly superior to placebo for reducing the severity of headache pain in both studies, and in relieving nausea in Study 2. The onset of significant efficacy with dihydroergotamine nasal spray compared to that with placebo for both severity of headache pain and relief of nausea occurred at 1 hour in Study 2 and at 3 hours in Study 1. Dihydroergotamine nasal spray was also significantly superior to placebo for the relief of headache pain in both studies. Based on the physicians' global evaluations of treatment efficacy for headache pain, 71% of the dihydroergotamine-treated patients in Study 2 and 59% of their counterparts in Study 1 were considered to be responders. The dihydroergotamine-treated patients had less newly-occurring vomiting than the placebo-treated patients. The majority of adverse events reported by the dihydroergotamine-treated patients were nasopharyngeal. The results demonstrate the efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the treatment of acute migraine attacks.

Acute Disease↗
PubMed1996

Acute treatment of migraine with dihydroergotamine nasal spray. Dihydroergotamine Working Group.

BACKGROUND: Despite the benefits of antimigraine medications for patients with migraines, parenteral administration of these drugs has certain disadvantages for at-home patient use. OBJECTIVE: To examine the safety and efficacy of an intranasal spray formulation of dihydroergotamine mesylate in the treatment of migraines. DESIGN: Double-blind, placebo-controlled trial in patients with migraines. SETTING: Both private and institutional practice. PATIENTS: A total of 348 patients with a diagnosis of migraine according to International Headache Society criteria were recruited; 310 patients qualified for participation. INTERVENTIONS: Patients self-administered either 2 mg of dihydroergotamine mesylate, 3 mg of dihydroergotamine mesylate, or a placebo for each of 2 moderate to severe migraine headaches using a nasal spray apparatus. MAIN OUTCOME MEASURES: Patients rated pain severity, functional ability, headache pain relief, incidence and severity of nausea, and the incidence of vomiting, photophobia, and phonophobia prior to treatment (base-line) and again at 0.5, 1, 2, 3, and 4 hours after treatment. Recurrences of headache pain within 24 hours were also noted. RESULTS: Self-administration of dihydroergotamine resulted in significant increases in pain relief and functional ability and significant decreases in pain intensity and nausea compared with the placebo. Among patients treated with 2 mg of dihydroergotamine mesylate, 27% considered their migraine resolved (ie, no pain or mild pain) as early as 30 minutes after treatment. By 4 hours after treatment, 70% of these patients' headaches were resolved. Headache pain returned within 24 hours in only 14% of patients whose headaches had been resolved. No serious adverse effects of dihydroergotamine treatment were observed, and the adverse events that did occur were primarily related to the route of administration. The 2-mg dihydroergotamine mesylate dose provided slightly superior pain relief and was associated with fewer adverse events compared with the 3-mg dihydroergotamine mesylate dose. CONCLUSIONS: The present results suggest that intranasal administration of dihydroergotamine represents an important new therapeutic option for migraine sufferers.

Acute Disease↗
PubMedDate not supplied

The influence of dihydroergotamine on adenosine-induced and reactive coronary vasodilation. Interaction of dihydroergotamine and coronary vasodilation.

The influence of dihydroergotamine on adenosine-induced and reactive vasodilation after long and short periods of coronary artery occlusion was investigated in thoracotomized dogs. Adenosine-induced vasodilation (intracoronary administration) and vasodilation after long periods of coronary artery occlusion (25-35 beats) were similarly influenced, i.e. decreased by the i.v. administration of 10 mug/kg dihydroergotamine. By contrast vasodilation after short periods of coronary artery occlusion (4-7 beats) tended to be increased. This difference in response is thought to arise from two distinct mechanisms of coronary vasodilation after coronary artery occlusion depending on the duration of the occlusion period. The vasodilation after short periods of coronary artery occlusion possibly corresponds to physiological autoregulation. With longer periods of coronary artery occlusion an additional, consecutive mechanism is called into action.

Adenosine↗
PubMed1977

[Quantitative assessment of drug-induced prophylaxis of postoperative thromboembolism. Comparison of frequencies of deep vein thrombosis and pulmonary embolism using acetylsalicylic-acid, dextran, dihydroergotamine, low-dose heparin and the fixed combination of heparin and dihydroergotamine (author's transl)].

2136 patients in general surgery, gynaecology and urology were investigated by the 125I-fibrinogen-uptake-test for detection of postoperative deep vein thrombosis (DVT). They received at random one of low-dose heparin, dihydroergotamine, the fixed combination of both drugs (Heparin-Dihydergot), low molecular weight dextran and acetylsalicylic-acid (ASS). When DVT was detected repeated lung perfusion scintigraphies were carried out for diagnosis of embolic pulmonary perfusion defects. Results demonstrate the outstanding effect of Heparin-Dihydergot, which is not only 2-3 times better than the anti-thrombotic standard low-dose heparin but also eliminates almost completely the risk of postoperative embolism. The preventive efficacy of ASS and dextran must be considered to be poor and not comparable to that obtained when using heparin, dihydroergotamine or the combination. Now Heparin-Dihydergot is the new standard with which all prophylactic procedures should be compared.

Adult↗
PubMed1983

The pharmacokinetics and bioavailability of subcutaneously administered dihydroergotamine, heparin and the dihydroergotamine-heparin combination.

Subcutaneously administered dihydroergotamine (DHE) becomes rapidly and completely available to the human systemic circulation, with peak plasma levels of 1.4-3.5 ng/mL/mg achieved in less than 1 h. The elimination of DHE from plasma is biphasic, t 1/2 alpha = 1h, t 1/2 beta = 4-5 h. DHE exhibits linear dose proportionality. Coadministration of heparin results in a statistically significant increase of 25% in the area under the plasma level/time curve for DHE (bioavailability). Coinjection of DHE and heparin in the same subcutaneous site furthermore causes a decrease in the rate of DHE absorption by 63%, resulting in delayed time to peak (by 110%) and reduced peak levels (by 15%) of DHE. In contrast, there is no effect by coadministered DHE on heparin pharmacokinetic parameters. Heparin peak plasma levels (0.3 I.U./mL by activated factor X, 0.1 I.U./mL by protamine titration with a 15,000 I.U. s.c. bolus) are achieved in 3.6 h. Pharmacokinetic analysis suggests that the subcutaneous route of administration provides only 19% of the bioavailable heparin that would be obtained following administration of an equipotent intravenous dose. DHE-heparin formulated for injection in combination demonstrates systemic availability identical to that of the two components injected separately, but with a reduced rate of absorption for the DHE component and a corresponding attenuation of fluctuations in steady state DHE levels.

Adult↗
PubMed2003

Dihydroergotamine and its metabolite, 8'-hydroxy-dihydroergotamine, as 5-HT1A receptor agonists in the rat brain.

1 In addition to stopping migraine attacks, dihydroergotamine (DHE) is an efficient drug for migraine prophylaxis. Whether 5-HT(1A) receptors could contribute to the latter action was assessed by investigating the effects of DHE and its metabolite, 8'-OH-DHE, on these receptors in the rat brain. 2 Membrane binding assays with [(3)H]8-OH-DPAT and [(3)H]WAY 100635 as radioligands showed that both DHE (IC(50)=28-30 nM) and 8'-OH-DHE (IC(50)=8-11 nM) are high-affinity 5-HT(1A) receptor ligands. 3 Both DHE and 8'-OH-DHE enhanced the specific binding of [(35)S]GTP-gamma-S to the dorsal raphe nucleus and the hippocampus in brain sections, but to a lower extent than 5-carboxamido-tryptamine (5-CT) in the latter area. 4 Both DHE (EC(50)=10.9+/-0.3 nM) and 8'-OH-DHE (EC(50)=30.4+/-0.8 nM) inhibited the firing of serotoninergic neurons in the dorsal raphe nucleus within brain stem slices. 5 Intracellular recording showed that 8'-OH-DHE was more potent than DHE to hyperpolarize CA1 pyramidal cells in rat hippocampal slices. 6 Both the stimulatory effects of DHE and 8'-OH-DHE on [(35)S]GTP-gamma-S binding and their electrophysiological effects were completely prevented by the selective 5-HT(1A) receptor antagonist WAY 100635. 7 As expected of 5-HT(1A) receptor partial agonists, DHE and 8'-OH-DHE prevented any subsequent hyperpolarization of CA1 pyramidal cells by 5-HT or 5-CT. 8 Through their actions at 5-HT(1A) auto- (in the dorsal raphe nucleus) and hetero-(notably in the hippocampus) receptors, DHE, and even more its metabolite 8'-OH-DHE, can exert both an inhibitory influence on neuronal excitability and anxiolytic effects which might contribute to their antimigraine prophylactic efficiency.

Animals↗
PubMed1996

Human pharmacokinetics of dihydroergotamine administered by nasal spray.

OBJECTIVES: A nasal spray of dihydroergotamine was developed for the treatment of migraine headaches, and pharmacokinetic studies were scheduled to evaluate the bioavailability of dihydroergotamine by this new route of administration. METHODS: Nine studies were performed with dihydroergotamine administered by nasal spray to evaluate the bioavailability of the nasal route versus the intramuscular route, the linearity of the kinetics, the interindividual and intraindividual variations, and the influence of different factors. RESULTS: Nasally administered dihydroergotamine (1 mg) becomes rapidly available to the systemic circulation, with peak plasma levels of 1 ng/ml achieved in 0.9 hour. The relative bioavailability versus intramuscular route is 38.4%. Dihydroergotamine administered by the nasal route exhibits linear dose proportionality (1 to 4 mg). Intraindividual variations of bioavailability evaluated for a 1-year period were higher (29%) than those found for the intramuscular route (20%) but comparable to the oral route. Interindividual variations for bioavailability were greater (25% versus 14% by the intramuscular route) but comparable to the oral route. Caffeine contained in the nasal solution (1%) had no effect on the absorption. Vasomotor phenomena, which could also affect the nasal mucosa during a migraine headache, do not modify the bioavailability. The constriction of the nasal mucosa by fenoxazoline leads to a slight decrease (-15%) in the bioavailability. The presence of acute viral rhinitis did not result in any change in dihydroergotamine nasal absorption compared with the normal state of the nasal mucosa. From a pharmacokinetic point of view, nasally administered dihydroergotamine can be given, without risk of overdose, to patients receiving long-term oral dihydroergotamine medication. CONCLUSION: These results show the reliability and reproducibility of this route of dihydroergotamine administration adapted for the treatment of migraine headaches.

Acute Disease↗
PubMed1996

A double-blind study of subcutaneous dihydroergotamine vs subcutaneous sumatriptan in the treatment of acute migraine.

OBJECTIVE: To assess the efficacy and tolerability of subcutaneous dihydroergotamine mesylate (DHE-45) vs subcutaneous sumatriptan succinate (Imitrex) for the treatment of acute migraine with or without aura. DESIGN: Double-blind, randomized trial with parallel treatment arms. SETTING: Clinics and private neurology practices. SUBJECTS: Patients of either sex, with migraine with or without aura, between the ages of 18 and 65 years. INTERVENTIONS: Patients with moderate or severe head pain were randomized to receive either 1 mg of subcutaneous dihydroergotamine mesylate or 6 mg of subcutaneous sumatriptan succinate. Patients rated head pain, functional ability, nausea, and vomiting at baseline and at 0.5, 1, 2, 4, and 24 hours after the injection. Presence or absence of headache at 3 hours was calculated from collected data. If pain persisted after 2 hours, a second injection of the same study medication was allowed, and self-ratings were repeated 30 and 60 minutes later. Follow-up data were collected at 24 hours. MAIN OUTCOME MEASURES: Relief of head pain and recurrence of successfully treated headache. RESULTS: There were 295 evaluable patients. At 2 hours, 73.1% of the patients treated with dihydroergotamine and 85.3% of those treated with sumatriptan had relief (P = .002). There was no statistical difference in headache relief between the groups at 3 or 4 hours. Headache relief was achieved by 85.5% of those treated with dihydroergotamine and by 83.3% of those treated with sumatriptan by 4 hours. By 24 hours 89.7% of dihydroergotamine-treated patients and 76.7% of sumatriptan-treated patients had relief (P = .004). Headache recurred within 24 hours after treatment in 45% of the sumatriptan-treated patients and in 17.7% of the dihydroergotamine-treated patients (P < or = .001). CONCLUSIONS: Both sumatriptan and dihydroergotamine were effective in aborting migraine headaches. Headache recurrence was two and a half time as likely with sumatriptan as with dihydroergotamine.

Acute Disease↗
PubMed1984

Elucidation of the structure and receptor binding studies of the major primary, metabolite of dihydroergotamine in man.

The plasma concentrations and urinary excretion of dihydroergotamine and its metabolites have been measured after a single oral administration of 3 mg tritium-labelled drug to 6 male volunteers. The plasma level of non-volatile radioactivity declined biphasically with alpha- and beta-phase half-lives of 2.1 h and 32.3 h, respectively. The peak plasma concentration was reached within 3.2 h. Urinary excretion of total non-volatile radioactivity was low, amounting to 1.0% of the dose. The parent drug and four metabolites could be quantitated in urine and plasma samples. Metabolite 4 (8'-hydroxy-dihydroergotamine) was isolated from incubates of rat and monkey liver microsomal preparations. In human liver microsomal incubates, metabolite 4 was shown to be the primary metabolite of dihydroergotamine. In receptor binding studies performed with mammalian brain preparations, metabolite 4 had IC50-values at 6 monoaminergic binding sites similar to those of dihydroergotamine. Thus, it appears that the active principle consists at least of dihydroergotamine and its 8'-hydroxy derivative. As the concentration of metabolite 4 exceeded 5-7 times that of dihydroergotamine in urine and plasma, the bioavailability of dihydroergotamine should be reevaluated, taking into account the plasma concentrations of the parent drug and of its active metabolite, 8'-hydroxy-dihydroergotamine.

Animals↗
PubMed1984

Investigation of the venoconstrictor effect of 8' hydroxydihydroergotamine, the main metabolite of dihydroergotamine, in man.

The time course of the venoconstrictor effect of dihydroergotamine and its main metabolite 8' hydroxy-dihydroergotamine was investigated in a placebo-controlled study in seven healthy male volunteers, after direct local infusion of 0.08 and 0.4 micrograms into superficial hand veins. Both dihydroergotamine and 8' hydroxy-dihydroergotamine elicited a similar, marked venoconstrictor effect. The time course of the venoconstrictor action was similar for both compounds; about one third of the effect was present at the end of the infusion, which lasted for 10 min, and it took about a further 20 min for the effect to reach its maximum. The effect then remained fairly constant for the rest of the period of observation of 180 min from the start of the infusion. The data indicate that the pharmacological activity of oral dihydroergotamine is due not only to the unchanged drug but also to its main metabolite, 8' hydroxy-dihydroergotamine, which occurs in plasma in concentrations about 5-7 times higher than those of dihydroergotamine itself. The absolute bioavailability of unchanged dihydroergotamine, therefore, does not reflect the markedly higher bioavailability of pharmacologically active drug.

Adult↗
PubMed2005

Parenteral dihydroergotamine for acute migraine headache: a systematic review of the literature.

STUDY OBJECTIVE: Many therapies are used in the treatment of acute migraine headache, with little agreement on effectiveness. This systematic review is designed to determine the effectiveness of parenteral dihydroergotamine in reducing pain, nausea, and relapse for episodes of acute migraine in adults. METHODS: Randomized controlled trials were identified using MEDLINE, EMBASE, other computerized databases, hand searching, bibliographies, and contacts with industry and authors. Studies in which dihydroergotamine (alone or in combination with an antiemetic) was compared with placebo or any other common migraine therapy were considered. Relevance, inclusion, and study quality were assessed independently by 2 reviewers. RESULTS: From 281 potentially relevant abstracts, 11 studies met the inclusion criteria. Solitary dihydroergotamine use was compared to sumatriptan and phenothiazines in 3 studies; results failed to demonstrate a significant benefit of dihydroergotamine over these therapies. In 8 combination treatment studies, heterogeneity in study methodology prevented statistical pooling. However, dihydroergotamine administered with an antiemetic was as effective as or more effective than meperidine, valproate, or ketorolac across all pain, nausea, and relapse outcomes reported in all studies. CONCLUSION: This evidence suggests that dihydroergotamine is not as effective as sumatriptan or phenothiazines as a single agent for treatment of acute migraine headache; however, when administered with an antiemetic, dihydroergotamine appears to be as effective as opiates, ketorolac, or valproate. Given its nonnarcotic properties, parenteral dihydroergotamine combined with an antiemetic should be considered as effective initial therapy in clinical practice.

Adult↗
PubMed1984

Dihydroergotamine-heparin prophylaxis of postoperative deep vein thrombosis. A multicenter trial. The Multicenter Trial Committee.

In a large, prospective, multicenter investigation of the prophylaxis of deep vein thrombosis (DVT) in patients undergoing elective abdominal, pelvic, and thoracic surgery, 880 patients were randomized into five treatment groups: those receiving (1) dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 5,000 IU; (2) dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 2,500 IU; (3) heparin sodium, 5,000 IU alone; (4) dihydroergotamine mesylate, 0.5 mg alone; or (5) placebo. Treatment was initiated preoperatively and continued twice daily for five to seven days. Daily radiofibrinogen uptake tests revealed the following DVT rates: Dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 5,000 IU, 9.4%; dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 2,500 IU, 16.8%; heparin sodium, 5,000 IU alone, 16.8%; dihydroergotamine mesylate, 0.5 mg alone, 19.4%; and placebo, 24.4%. Dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 5,000 IU, was significantly superior to all other treatments. Adverse drug experiences did not differ significantly between groups and consisted primarily of postoperative bleeding (2% to 3%), injection site hematoma (6% to 12%), and wound hematoma (1% to 3%).

Adult↗
PubMed1987

Effects of calcium channel blockers on the contractile response to dihydroergotamine in isolated human femoral veins.

Contractions induced in spirally cut human postmortem femoral veins by dihydroergotamine, noradrenaline, or 5-hydroxytryptamine (5-HT) were measured isometrically. The influence of calcium channel blockers (verapamil, diltiazem and nifedipine), lanthanum chloride and withdrawal of external calcium on the contractile response of veins to dihydroergotamine was investigated. The agonists noradrenaline and 5-HT were studied in comparison. Verapamil and nifedipine up to a concentration of 1 mumol/l caused a shift to the right of the cumulative concentration-response curves for noradrenaline and 5-HT with a reduction of the maximum contraction. Diltiazem affected the contractile response to 5-HT slightly. The venocontractions induced by dihydroergotamine at a concentration of 0.03 mumol/l were inhibited by the calcium channel blockers in a concentration-dependent manner. Verapamil was most effective, followed by nifedipine and diltiazem. In dihydroergotamine-precontracted veins nifedipine produced a more pronounced relaxation than verapamil. Lanthanum chloride (5 mmol/l) inhibited the dihydroergotamine-induced contraction by about 90%. Exposure of veins to a calcium-free medium for 30 min resulted in an inhibition of the dihydroergotamine-induced venocontraction by more than 90%. The addition of calcium ions to the medium caused an increase in the contraction with a maximum which closely resembled that of the control. The present studies demonstrate that the contractile response of human femoral veins to dihydroergotamine depends to a great extent on extracellular calcium. However, the calcium channel blockers verapamil, diltiazem and nifedipine, inhibit the agonist-induced venocontractions in part only.

Adult↗
PubMed1983

Thromboembolic prophylaxis with dihydroergotamine-heparin in abdominal surgery. A controlled, randomized study.

The prophylactic affect of dihydroergotamine-heparin (0.5 mg dihydroergotamine plus 5,000 units of heparin administered twice daily) against postoperative thromboembolic complications after gastrointestinal surgery was compared with the affect of 5,000 units of heparin administered three times daily in a controlled, randomized study. Fifty patients received the dihydroergotamine and heparin combination twice daily and 50 patients received 5,000 units of heparin three times daily. The two groups were comparable with respect to age, sex, body weight, and type of operation. The presence or absence of deep venous thrombosis in the legs was determined postoperatively by the radiofibrinogen uptake test. The frequency of deep venous thrombosis in the dihydroergotamine and heparin group was 12 percent compared with 18 percent in the heparin group (0.1 greater than p greater than 0.05). Wound hematoma developed in two patients in the heparin group and in one patient in the dihydroergotamine and heparin group (4 and 2 percent, respectively). No other hemorrhagic complications occurred. By combining heparin with dihydroergotamine it is possible to reduce the daily heparin dose by one third and still obtain the same level of prophylaxis against thromboembolism. The frequency of bleeding complications was very low in both groups, since only one wound hematoma occurred in the dihydroergotamine and heparin group and two in the heparin group.

Abdomen↗
PubMed1989

Fixed combinations of low-molecular weight or unfractionated heparin plus dihydroergotamine in the prevention of postoperative deep vein thrombosis.

A prospective, double-blind, randomized, controlled clinical trial compared the efficacy and safety of fixed combinations of low-molecular weight heparin or standard unfractionated heparin plus dihydroergotamine mesylate in the prevention of deep vein thrombosis in high-risk patients undergoing elective major abdominal surgery. Two hundred patients, with a mean age of 66.6 years and almost half with malignancy, were allocated to receive either 5,000 IU unfractionated heparin plus 0.5 mg dihydroergotamine mesylate twice daily or 1,500 IU low-molecular weight heparin plus 0.5 mg dihydroergotamine mesylate once daily together with one placebo injection per day. Treatment was commenced 2 hours preoperatively and continued for at least 7 days. The incidence of deep vein thrombosis, determined by radiolabelled fibrinogen uptake and phlebography, was 11 percent in the unfractionated heparin plus dihydroergotamine mesylate group and 11.4 percent in the low-molecular weight heparin and dihydroergotamine mesylate group. Neither these figures nor those for major proximal thrombi proved significantly different. Of the four parameters used to assess hemorrhagic complications, only the decrease in postoperative hemoglobin levels in the low-molecular weight and dihydroergotamine mesylate group reached statistical significance. These results indicate that once-daily prophylaxis with a combination of low-molecular weight heparin and dihydroergotamine is safe, effective, and convenient in high-risk patients undergoing major abdominal surgery.

Adult↗