Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5-HT1B/1D receptors and alpha2-adrenoceptors. (1/61)

The antimigraine drugs methysergide, ergotamine and dihydroergotamine (DHE) produce selective vasoconstriction in the external carotid bed of vagosympathectomized dogs anaesthetized with pentobarbital and artificially respired, but the receptors involved have not yet been completely characterized. Since the above drugs display affinity for several binding sites, including alpha-adrenoceptors and several 5-HT1 and 5-HT2 receptor subtypes, this study has analysed the mechanisms involved in the above responses. Intracarotid (i.c.) infusions during 1 min of methysergide (31-310 microg min(-1)), ergotamine (0.56-5.6 microg min(-1)) or DHE (5.6-31 microg min(-1)) dose-dependently reduced external carotid blood flow (ECBF) by up to 46+/-4, 37+/-4 and 49+/-5%, respectively. Blood pressure and heart rate remained unchanged. The reductions in ECBF by methysergide were abolished and even reversed to increases in animals pre-treated with GR127935 (10 microg kg(-1), i.v.). The reductions in ECBF by ergotamine and DHE remained unchanged in animals pre-treated (i.v.) with prazosin (300 microg kg(-1)), but were partly antagonized in animals pre-treated with either GR127935 (10 or 30 microg kg(-1)) or yohimbine (1000 microg kg(-1)). Pre-treatment with a combination of GR127935 (30 microg kg(-1)) and yohimbine (1000 microg kg(-1)) abolished the responses to both ergotamine and DHE. The above doses of antagonists were shown to produce selective antagonism at their respective receptors. These results suggest that the external carotid vasoconstrictor responses to methysergide primarily involve 5-HT1B/1D receptors, whereas those to ergotamine and DHE are mediated by 5-HT1B/1D receptors as well as alpha2-adrenoceptors.  (+info)

Secretory responses to sympathetic stimulation of the cat's salivary glands in a state of resting secretion. (2/61)

The secretory effect of sympathetic stimulation on the cat's submaxillary gland was augmented greatly when studied against a background of slow secretion evoked by parasympathetic stimulation at a low frequency and imitating the slow resting secretion normally present in the waking state. The sympathetic secretory threshold was markedly lowered, and even at low frequencies sympathetic stimulation caused a large, well-maintained response. After an alpha-adrenoceptor blocking drug sympathetic stimulation alone lost its secretory effect, but during resting secretion part of the accelerating effect was found to remain; this effect was elicited via beta-adrenoceptors. A marked secretory effect of sympathetic stimulation was also obtained during resting secretion in the parotid gland, where the sympathetic secretory effect is normally very small.  (+info)

Newer intranasal migraine medications. (3/61)

Two new intranasal migraine medications, sumatriptan and dihydroergotamine mesylate, may offer specific advantages for patients who are seeking alternatives to various oral or parenteral migraine abortive therapies. Placebo-controlled clinical studies demonstrate that both intranasal forms are effective in relieving migraine headache pain, but published clinical trial information comparing these two intranasal medications with current abortive therapies is lacking. Both agents are generally well tolerated by patients, with the exception of mild, local adverse reactions of the nose and throat.  (+info)

Alternate numbness in the upper extremities as the initial symptom of basilar migraine: an electrophysiological evaluation using EEG power topography. (4/61)

A case of basilar migraine (BM) with alternate numbness as the initial symptom is described. The patient's chief complaint was alternate numbness in the right and left upper extremities. After angiography the patient fell into a drowsy state, followed by excitation, and finally confusion. The EEG power topography showed slow alpha, theta and delta power in the right occipital area, and alternatively in the right and left parietal area. These findings suggest that the cause of BM is not only based on a vasoconstriction mechanism, but also cortical spreading depression. BM should be suspected as a cause of sensory symptoms.  (+info)

Dihydroergotamine: discrepancy between arterial, arteriolar and pharmacokinetic data. (5/61)

AIMS: To investigate the peripheral vascular effects and pharmacokinetics of dihydroergotamine (DHE) 0.5 mg after a single subcutaneous administration in humans. METHODS: A double-blind, placebo-controlled cross-over study was performed in 10 healthy male subjects. A wash-out period of 2 weeks separated the two study periods. During each period, just before and at regular intervals after drug administration, vascular measurements were performed and venous blood samples were drawn. Vessel wall properties were assessed at the brachial artery, by ultrasound and applanation tonometry. Blood pressure and heart rate were recorded with an oscillometric device. Forearm blood flow was measured with venous occlusion plethysmography. For all parameter-time curves the area under the curve (AUC) was calculated. Differences in AUC after placebo and DHE (DeltaAUC) were analysed and the time-course of the difference assessed. DHE pharmacokinetics were analysed according to a two-compartment open model with an absorption phase. RESULTS: AUC for blood pressure, heart rate and forearm vascular resistance did not change after DHE. Brachial artery diameter and compliance decreased (P < 0.01); DeltaAUC (95% confidence interval) equalled -8.81 mm h (-12.97/-4.65) and -0.98 mm2 kPa(-1) h (-1.61/-0.34), respectively. Diameter decreased (P < 0.05) from 1 until 24 h after DHE (peak decrease 9.7% at 10 h); compliance from 2 until 32 h (24.8% at 2 h). Time to reach maximum plasma concentration of DHE averaged 0.33 +/- 0.08 h (+/- s.e.mean); terminal half-life was 5.63 +/- 1.15 h. CONCLUSIONS: DHE decreased diameter and compliance of the brachial artery whereas forearm vascular resistance remained unchanged. Thus, DHE acts on conduit arteries without affecting resistance arteries. Furthermore, a discrepancy was demonstrated between the plasma concentrations of DHE which rapidly reach peak levels and quickly decline, and its long lasting vasoconstrictor activity.  (+info)

Haemodynamic effects of three doses of dihydroergotamine during spinal anaesthesia. (6/61)

We performed a randomized study comparing the haemodynamic effects of three doses of the vasopressor dihydroergotamine (DHE) (5, 10 and 15 microg x kg(-1)) in 30 ASA 1 and 2 patients, aged 53-87 yr, undergoing spinal anaesthesia. Non-invasive systolic arterial pressure (SAP), heart rate and central venous pressure (CVP) were recorded continuously for 25 min. Intravenous fluids were withheld during this period. All three doses of DHE reversed the lowering effects of spinal anaesthesia on SAP and CVP (P<0.0001), and these effects were smooth in onset and sustained. Whereas the lowest (5 microg x kg(-1)) dose restored SAP and CVP to near prespinal values, the higher (10 and 15 microg x kg(-1)) doses resulted in above-baseline increases in SAP of 7% and in CVP of 2.7 cm H2O (P<0.05). The haemodynamic profile of DHE makes it a useful agent for managing hypotension during spinal anaesthesia. A dose of 5-10 microg x kg(-1) is recommended.  (+info)

Cluster headaches associated with vascular malformations. (7/61)

A vascular malformation was demonstrated in a migrainous female who had developed cluster headaches. The patient responded well to oral dihydroergotamine 1 mg twice daily.  (+info)

The antimigraine 5-HT 1B/1D receptor agonists, sumatriptan, zolmitriptan and dihydroergotamine, attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain. (8/61)

1. Peripheral lesion to the trigeminal nerve may induce severe pain states. Several lines of evidence have suggested that the antimigraine effect of the triptans with 5-HT(1B/1D) receptor agonist properties may result from inhibition of nociceptive transmission in the spinal nucleus of the trigeminal nerve by these drugs. On this basis, we have assessed the potential antinociceptive effects of sumatriptan and zolmitriptan, compared to dihydroergotamine (DHE), in a rat model of trigeminal neuropathic pain. 2. Chronic constriction injury was produced by two loose ligatures of the infraorbital nerve on the right side. Responsiveness to von Frey filament stimulation of the vibrissal pad was used to evaluate allodynia. 3. Two weeks after ligatures, rats with a chronic constriction of the right infraorbital nerve displayed bilateral mechanical hyper-responsiveness to von Frey filament stimulation of the vibrissal pad with a mean threshold of 0.38+/-0.04 g on the injured side and of 0.43+/-0.04 g on the contralateral (left) side (versus > or =12.5 g on both sides in the same rats prior to nerve constriction injury). 4. Sumatriptan at a clinically relevant dose (100 microg kg(-1), s.c.) led to a significant reduction of the mechanical allodynia-like behaviour on both the injured and the contralateral sides (peak-effects 6.3+/-1.1 g and 4.4+/-0.7 g, respectively). A more pronounced effect was obtained with zolmitriptan (100 microg kg(-1), s.c.) (peak-effects: 7.4+/-0.9 g and 3.2+/-1.3 g) whereas DHE (50-100 microg kg(-1), i.v.) was less active (peak-effect approximately 1.5 g). 5. Subcutaneous pretreatment with the 5-HT(1B/1D) receptor antagonist, GR 127935 (3 mg kg(-1)), prevented the anti-allodynia-like effects of triptans and DHE. Pretreatment with the 5-HT(1A) receptor antagonist, WAY 100635 (2 mg kg(-1), s.c.), did not alter the effect of triptans but significantly enhanced that of DHE (peak effect 4.3+/-0.5 g). 6. In a rat model of peripheral neuropathic pain, which consisted of a unilateral loose constriction of the sciatic nerve, neither sumatriptan (50-300 microg kg(-1)) nor zolmitriptan (50-300 microg kg(-1)) modified the thresholds for paw withdrawal and vocalization in response to noxious mechanical stimulation. 7. These results support the rationale for exploring the clinical efficacy of brain penetrant 5-HT(1B/1D) receptor agonists as analgesics to reduce certain types of trigeminal neuropathic pain in humans.  (+info)