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Migraine and cluster headache--their management with sumatriptan: a critical review of the current clinical experience.

Sumatriptan is a potent and selective agonist at the vascular 5HT1 receptor which mediates constriction of certain large cranial blood vessels and/or inhibits the release of vasoactive neuropeptides from perivascular trigeminal axons in the dura mater following activation of the trigeminovascular system. The mode of action of this drug in migraine and cluster headache is discussed. On the basis of a detailed review of all published trials and available data from post-marketing studies, the efficacy, safety, tolerability and the place of oral and subcutaneous sumatriptan in the treatment of both conditions are assessed. A number of double-blind clinical trials have demonstrated that sumatriptan 100 mg administered orally is clearly superior to placebo in the acute treatment of migraine headache and achieves significantly greater response rates than ergotamine or aspirin. In other studies, 70 to 80% of patients receiving sumatriptan 6 mg sc experienced relief of migraine headaches by 1 or 2 h after administration, and patients consistently required less rescue medication for unresolved symptoms. Sumatriptan was also effective in relieving associated migraine symptoms like nausea and vomiting. Sumatriptan was equally effective regardless of migraine type or duration of migraine symptoms. Overall, approximately 40% of patients who initially responded to oral or subcutaneous sumatriptan experienced recurrence of their headache usually within 24 h, effectively treated by a further dose of this drug. In 75% of patients with cluster headache treated with sumatriptan 6 mg sc, relief was achieved within 15 min. Based on pooled study data, sumatriptan is generally well tolerated and most adverse events are transient. Adverse events following oral administration include nausea, vomiting, malaise, fatigue and dizziness. With the subcutaneous injection, injection site reactions occur in approximately 30%. Chest syumptoms are reported in 3 to 5% but have been associated with myocardial ischaemia only in rare isolated cases. The recommended dosage of sumatriptan at the onset of migraine symptoms is 100 mg orally or 6 mg subcutaneously. The recommended dosage for cluster headache is 6 mg sumatriptan sc. Sumatriptan must not be given together with vasoconstrictive substances, e.g., ergotamines, or with migraine prophylactics with similar properties, e.g., methysergide. Sumatriptan should not be given during the migraine aura. It is contraindicated in patients with ischaemic heart disease, previous myocardial infarction, Prinzmetal (variant) angina and uncontrolled hypertension.

Clinical Trials as Topic↗

Transformed migraine is a cause of chronic daily headaches.

Chronic daily headaches (CDH) consist of episodes of head pain occurring daily; more than 15 days each month; often associated with a history of migraine, with or without aura; or with a history of tension-type headaches occurring alone or both occurring together. Chronic daily headaches are frequently associated with rebound headaches after ergotamine, barbiturate, caffeine, and analgesic abuse. We previously reported that migraineurs with typical intermittent headaches exhibited excessive cerebral cortical vasodilation after oral acetazolamide which usually precipitated and reproduced their typical headaches. In the present study, cerebral vasodilator responses were tested by measuring changes in local cerebral blood flow (Delta LCBF) utilizing xenon-contrasted CT scanning, before and after oral administration of 14.3 mg/kg of acetazolamide, in 11 patients with CDH. The results were compared with 12 age-matched typical migraineurs, with and without aura, who had a history of migraine attacks occurring at intervals of 1 month or longer. Global and subcortical gray and white matter Delta LCBFs were quantitated and compared between both groups. After acetazolamide, Delta LCBF increased in cortical gray matter by 11.8% among patients with CDH and by 16.7% among migraineurs, with no significant differences between groups. Typical migraine attacks were provoked by acetazolamide in 9 patients (82%) with CDH and in 11 (92%) migraineurs with intermittent headaches. These observations are taken as evidence that at least 82% of patients with CDH have transformed migraine as judged by the provocation by acetazolamide of typical migraine attacks associated with excessive Delta LCBF increases. Serotonin agonists should be considered in the treatment of CDH to avoid ergotamine, caffeine, barbiturate, and analgesic abuse.

Acetazolamide↗

[Erogotism as a cuase of abnormal peripheral arterial flow (author's transl)].

Ergotism is seen rarely as a complication of the treatment of migraine with drugs containing egotamine. The prognosis is good if the disease is recognised at an early stage and ergotamine medication is discontinued. A case of ergotism studied angiographically is described. The patient was a 46-year old woman who developed severe vascular spasm in pelvic and lower limb arteries within four weeks of taking 100 mg. erotamine tartrate. The changes disappeared completely once the ergotamine preparation was stopped.

Angiography↗

[Tension headache--a review].

Tension headache (TH) is an ill-defined headache syndrome, characterized by bilateral, daily headaches with fronto-occipital localisation. TH is often accompanied by a migraine and an abuse of analgesics and/or ergotamine. In the etiology of TH vascular, muscular and psychogenic factors are assumed. Floating transitions to common migraine are discussed. The increased muscle tension is not specific for TH, but more probably a consequence of TH. In addition a decrease of the pain threshold with a deficiency of the antinociceptive system is supposed. The efficacy of tricyclic antidepressives in TH is based on potentiation of serotonergic and noradrenergic mechanisms and - besides their analgetic potencies - upon an increase of the pain threshold. TH prophylaxis is indicated if patients suffer from TH more than ten times per month. Medication are tricyclic antidepressives of the amitriptyline-type. Prophylaxis of TH can only be successful if a simultaneous abuse of analgesics and/or ergotamine is discontinued. In addition, EMG-biofeedback, as well as relaxation - and vasoconstriction training might be helpful in specific cases.

Diagnosis, Differential↗

Two members of a distinct subfamily of 5-hydroxytryptamine receptors differentially expressed in rat brain.

We report two serotonin (5-hydroxytryptamine, 5-HT) receptors, MR22 and REC17, that belong to the G-protein-associated receptor superfamily. MR22 and REC17 are 371 and 357 amino acids long, respectively, as deduced from nucleotide sequence and share 68% mutual amino acid identity and 30-35% identity with known catecholamine and 5-HT receptors. Saturable binding of 125I-labeled (+)-lysergic acid diethylamide to transiently expressed MR22 in COS-M6 cells was inhibited by ergotamine > methiothepin > 5-carboxamidotryptamine > 5-HT. For REC17, the rank of potency was ergotamine > 5-carboxamidotryptamine > methiothepin > methysergide > 5-HT. Both were insensitive to 5-HT1A, 5-HT1D or 5-HT2 serotonergic ligands [8-hydroxy-2-(di-n-propylamino)tetralin, sumatriptan, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]. The mRNAs encoding MR22 were detected in the CA1 region of hippocampus, the medial habenula, and raphe nuclei. In contrast, mRNAs encoding REC17 were found throughout the rat central nervous system. We propose that REC17 and MR22, designated as 5-HT5 alpha and 5-HT5 beta, represent a distinct subfamily of 5-HT receptors.

Amino Acid Sequence↗

D-Lysergyl peptide synthetase from the ergot fungus Claviceps purpurea.

The ergot fungus Claviceps purpurea produces the medically important ergopeptines, which consist of a cyclol-structured tripeptide and D-lysergic acid linked by an amide bond. An enzyme activity capable of non-ribosomal synthesis of D-lysergyl-L-alanyl-L-phenylalanyl-L-proline lactam, the non-cyclol precursor of the ergopeptine ergotamine, has been purified about 18-fold from the ergotamine-producing C. purpurea strain D1. Analysis of radioactively labeled enzyme-substrate complexes revealed a 370-kDa lysergyl peptide synthetase 1 (LPS 1) carrying the amino acid activation domains for alanine, phenylalanine, and proline. The activation of D-lysergic acid is catalyzed by a 140-kDa peptide synthetase (LPS 2) copurifying with LPS 1. LPS 1 and LPS 2 contain 4'-phosphopantetheine and bind their substrates covalently by thioester linkage. Kinetic analysis of the synthesis reaction revealed a Km of approximately 1.4 microM for both D-lysergic acid and its structural homolog dihydrolysergic acid, which is one to two orders of magnitude lower than the Km values for the other amino acids involved. The Km values for the amino acids reflect their relative concentrations in the cellular pool of C. purpurea. This may indicate that in in vivo conditions D-lysergyl peptide formation is limited by the D-lysergic acid concentration in the cell. In vitro, the multienzyme preparation catalyzes the formation of several different D-lysergyl peptide lactams according to the amino acids supplied. Specific antiserum was used to detect LPS 1 in various C. purpurea strains. In C. purpurea wild type, the enzyme was expressed at all stages of cultivation and in different media, suggesting that it is produced constitutively.

Amino Acids↗

HMO direct costs and health care resources use after implementation of a monthly limit on sumatriptan.

The health care costs and resource use of patients with migraine before and after a quantity limit on sumatriptan was introduced in an HMO were compared. A longitudinal, retrospective review of a medical claims database and a pharmacy claims database was conducted for two six-month periods before and after a monthly limit (four tablets or injections) on sumatriptan reimbursement was instituted at an independent practice association-model HMO in February 1997. Patients with at least one medical claim with a diagnosis code for migraine or at least two pharmacy claims for sumatriptan, methysergide, ergotamine, dihydroergotamine, or an ergotamine combination product in 1996 or 1997 were eligible for inclusion. A total of 557 patients were included in the analysis. Migraine-related medical costs and total medical costs increased 1.5% and 24.4%, respectively; neither change was statistically significant. Physician office visits related to migraine increased by 7.8%. The number of hospital admissions for the cohort increased from three to five, but hospital costs decreased by 55.0%. The overall costs of medications for migraine therapy decreased by 4.5%. There was an 8.2% increase in prescriptions for drugs to treat migraine but a 40.0% decrease in their cost, primarily because of decreased sumatriptan use. There was a 33.9% increase in prescriptions for medications that could be used as prophylaxis for migraine and a 49.6% increase in their cost. Implementation of a monthly limit on sumatriptan decreased an HMO's pharmacy costs but did not significantly alter migraine-related direct medical costs and health care resource use of patients with migraine.

Drug Costs↗

Quantitative determination of ergot alkaloids in biological fluids by radioimmunoassay.

1 Cross-reactivity of ergot alkaloids with an antiserum produced against lysergic acid conjugated with human serum, albumin was utilized to develop a radioimmunoassay for ergotamine, dihydroergotamine, dihydroergotoxine, ergometrine and methylergometrine in biological fluids. The antisera showed no cross-reactivity with simpler indole structures. 2 A procedure for extraction and concentration of alkaloids in biological fluids was developed. 3 The assay is sensitive for 1.8 ng/ml ergotamine, 1.5 ng/ml dihydroergotamine, 2.2 ng/ml dihydroergotoxine, 0.7 ng/ml ergotmetrine and 0.5 ng/ml methylergometrine. 4 The assay is sufficiently sensitive to permit the measurement of urine and plasma ergot alkaloid levels and it is suitable for determination in cases where a known ergot alkaloid is used.

Cross Reactions↗

Transformed migraine and medication overuse in a tertiary headache centre--clinical characteristics and treatment outcomes.

Studies suggest that a substantial proportion of headache sufferers presenting to headache clinics may overuse acute medications. In some cases, overuse may be responsible for the development or maintenance of a chronic daily headache (CDH) syndrome. The objectives of this study are to evaluate patterns of analgesic overuse in patients consulting a headache centre and to compare the outcomes in a group of patients who discontinued medication overuse to those of a group who continued the overuse, in patients with similar age, sex and psychological profile. We reviewed charts of 456 patients with transformed migraine (TM) and acute medication overuse defined by one of the following criteria: 1. Simple analgesic use (>1000 mg ASA/acetaminophen) > 5 days/week; 2. Combination analgesics use (caffeine and/or butalbital) > 3 tablets a day for > 3 days a week; 3. Opiate use > 1 tablet a day for > 2 days a week; 4. Ergotamine tartrate use: 1 mg PO or 0.5 mg PR for > 2 days a week. For triptans, we empirically considered overuse > 1 tablet per day for > 5 days per week. Patients who were able to undergo detoxification and did not overuse medication (based on the above definition) after one year of follow-up were considered to have successful detoxification (Group 1). Patients who were not able to discontinue offending agents, or returned to a pattern of medication overuse within one year were considered to have unsuccessful detoxification (Group 2). We compared the following outcomes after one year of follow-up: Number of days with headache per month; Intensity of headache; Duration of headache; Headache score (frequency x intensity). The majority of patients overused more than one type of medication. Numbers of tablets taken ranged from 1 to 30 each day (mean of 5.2). Forty-eight (10.5%) subjects took >10 tablets per day. Considering patients seen in the last 5 years, we found the following overused substances: Butalbital containing combination products, 48%; Acetaminophen, 46.2%; Opioids, 33.3%; ASA, 32.0%; Ergotamine tartrate, 11.8%; Sumatriptan, 10.7%; Nonsteroidal anti-inflammatory medications other than ASA, 9.8%; Zolmitriptan, 4.6%; Rizatriptan, 1.9%; Naratriptan, 0.6%. Total of all triptans, 17.8%. Of 456 patients, 318 (69.7%) were successfully detoxified (Group 1), and 138 (30.3%) were not (Group 2). The comparison between groups 1 and 2 after one year of follow-up showed a decrease in the frequency of headache of 73.7% in group 1 and only 17.2% in group 2 (P < 0.0001). Similarly, the duration of head pain was reduced by 61.2% in group 1 and 14.8% in group 2 (P < 0.0001). The headache score after one year was 18.8 in group 1 and 54 in group 2 (P < 0.0001). A total of 225 (70.7%) successfully detoxified subjects in Group 1 returned to an episodic pattern of migraine, compared to 21 (15.3%) in Group 2 (P < 0.001). More rigorous prescribing guidelines for patients with frequent headaches are urgently needed. Successful detoxification is necessary to ensure improvement in the headache status when treating patients who overuse acute medications.

Adolescent↗

The inhibitory action of noradrenaline and adrenaline on acetylcholine output by guinea-pig ileum longitudinal muscle strip.

1. Noradrenaline and adrenaline reduce the output of acetylcholine by the guinea-pig ileum longitudinal strip by up to 80%, both in resting conditions and after stimulation. The effect is graded with dose, and is detectable with noradrenaline 2 x 10(-7) g/ml. Adrenaline is approximately 4 times as active as noradrenaline, and its action after being washed out is more persistent.2. If resting output is high, both amines have a proportionately greater effect and their action, as dosage is increased, is to reduce resting output to a basal level, relatively constant from strip to strip, of about 10 ng/g/min.3. With stimulation, the effect of the amine is greater at low frequencies, when the output per volley is high, than at high frequencies. The effect is reduced by increasing the number of shocks delivered. There thus appears to be a basal output per volley, of the order of 1-2 ng/g/volley, which can be reached either by relatively rapid stimulation, by prolonged stimulation, or by treatment with these amines.4. If noradrenaline is applied during continued stimulation at 40/min, the depression of acetylcholine output during its presence is followed by an augmented output when the drug is withdrawn. The magnitude of this "overshoot" increases with the duration of noradrenaline exposure.5. Phenylephrine 4 mug/ml. and amphetamine 20 mug/ml. reduced the acetylcholine output, but isoprenaline 1 mug/ml., dopamine 1 mug/ml. and methoxamine 10 mug/ml. were ineffective.6. Phenoxybenzamine reduced the resting output and increased the stimulation output. Of the two other blocking agents examined, phentolamine had no effect on either resting or stimulation output and ergotamine transiently reduced stimulation output. The effect of phenoxybenzamine was not due to a reaction with either adrenoceptive or muscarinic receptors.7. Phenoxybenzamine, phentolamine and ergotamine abolished the effect of adrenaline and noradrenaline on both resting output and on output in response to stimulation.8. In strips obtained from animals treated with reserpine and guanethidine, a rise in resting acetylcholine output and in stimulation output at low frequencies was found. In these conditions, noradrenaline was still effective.9. Reducing the hydroxytryptamine content of the strips by treatment with p-chloro-(+/-)-phenylalanine did not significantly affect acetylcholine output.10. It is concluded that acetylcholine output by the nervous networks of the longitudinal strip is under the normal control of the sympathetic by a species of presynaptic inhibition mediated by alpha receptors. This implies that for a tissue under dual autonomic control, withdrawal of sympathetic control will lead to a parasympathetic response which is not only unopposed but also itself enhanced.

Acetylcholine↗

Myocardial ischemia related to ergot alkaloids: a case report and literature review.

Ergotamine tartrate and methysergide are widely used headache treatments with important vasoconstrictive properties. We report a 31-year-old man with cluster headaches who developed severe, prolonged myocardial ischemia following combination therapy with ergotamine tartrate and methysergide. We reviewed the cardiovascular complications of each agent alone and in combination. Given the pharmacologic similarity of these agents, we propose that they may have additive or synergistic cardiac toxicity, at least in vulnerable individuals. We recommend caution when these agents are used together.

Adolescent↗

Chronic daily headache: long-term prognosis following inpatient treatment with repetitive IV DHE.

We retrospectively studied the long-term (2-year) outcome of 50 consecutive patients admitted to our inpatient headache program because of chronic daily headache (CDH) associated with the overuse of analgesics, ergotamine, or both. They had been detoxified, given repetitive intravenous dihydroergotamine (IV DHE) and prophylactic medications as part of the program, and had become headache-free on this regimen. At the time of admission, 37 of the 50 patients had transformed migraine (TM), 12 had new daily persistent headache (NDPH), and 1 had chronic tension-type headache; 29 of the patients with TM, 7 of those with NDPH, and the single patient with chronic tension-type headache had coexistent migraine. Substances abused, alone or in combination, included: caffeine in 39 patients (av. 441 mg/d), acetaminophen in 32 (av. 2187 mg/d), aspirin in 24 (av. 1807 mg/d), ibuprofen in 9 (av. 1156 mg/d), narcotics in 7 (av. 10.1 mg morphine equivalents/d) and ergotamine in 11 (av. 2.3 mg/d). Twenty patients were using preventive medication at the time of admission. Follow-up evaluations were performed at 3, 6, 12, and 24 months after discharge. Forty-three patients were analyzed at 3 months. Of these, 44% had an excellent or good result and 28% a fair result; 3 were overusing analgesics. At 24 months, 39 patients were analyzed: 59% had a good or excellent result and 28% a fair result; 5 were overusing analgesics, 4 of whom were doing poorly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A comparison between placebo, pizotifen and 1-isopropyl-3-hydroxy-5-semicarbazono-6-oxo-2.3.5.6-tetrahydroindol (Divascan) in migraine prophylaxis.

The effects and side-effects in migraine prophylaxis of placebo, Divascan (1-isopropylnoradrenochrome--5--monosemicarbazone) and pizotifen were compared in a double-blind cross-over study. The dosage was for Divascan 15 mg a day and for pizotifen 3 mg a day. Data from the last 6 weeks of each test period of 8 weeks were used to assess the effect of the treatment. Thirty patients entered the trial. Data from 28 patients treated with placebo and Divascan and 27 patients treated with pizotifen were used for final evaluation. Pizotifen significantly reduced the number of migraine attacks, headache index and the consumption of ergotamine. Divascan also seemed to have effect. The consumption of ergotamine was reduced compared with placebo and there was a reduction, although not significant, of headache frequency and headache index. Pizotifen gave significantly larger reduction in headache frequency and headache index than Divascan and signficantly more patients stated a preference for pizotifen compared with Divascan. A good or very good effect was reported by 11 per cent of the patients on placebo, 39 per cent on Divascan and 70 per cent on pizotifen. Pizotifen had frequent side-effects, mainly drowsiness and weight gain, whereas Divascan in this respect did not differ from placebo. Physical examinations and laboratory investigations did not show any significant changes, apart from weight gain.

Adrenochrome↗

Cluster headache: a review.

Cluster headache is a rare headache entity that predominantly occurs in younger males. The clinical features are characterized by sudden attacks of unilateral excruciating pain localized periorbitally, associated with ipsilateral autonomic symptoms. The attacks occur in periods: clusters. The pathophysiology is still unknown. Such vasodilating substances as histamine, nitroglycerin and alcohol may provoke attacks. These substances may be used as diagnostic tests, but the interpretation of a negative result must be careful, as the attacks can not be induced in a refractory period after spontaneous occurrence, or at the beginning and end of cluster periods. As symptomatic treatment, ergotamine is the drug of first choice. High attack frequency may lead to overconsumption with ergotisme and further increased frequency. In such cases and for nocturnal attacks, oxygen inhalations represent an alternative. As prophylactic treatment ergotamine, methysergide, lithium and prednisone have proved efficacious. Most patients benefit from such treatment and may become virtually free from attacks. It is, therefore, important to differentiate this headache entity from classical migraine, common migraine and trigeminal neuralgia.

Cluster Headache↗

Effect of serotonin antagonists on the dextran-induced anaphylactoid reaction in the rat.

Dextran injected intravenously into rats causes a rapid lowering of the extent of activation of factor XII and of the plasma levels of prekallikrein and plasminogen, and at the same time a profound fall in blood pressure. The effects on these dextran-induced reactions of three serotonin antagonistic lysergic acid derivatives were studied in the rat: bromolysergic acid diethylamide (BOL 148), methysergide, and ergotamine. BOL 148 was found to be the only effective inhibitor of the blood pressure fall, possessing an inhibitory effect over the dose range 1.0-4.0 mg/kg intravenously. The finding supports the assumption that part of the dextran-induced blood pressure fall is mediated by serotonin through D-receptors. All three serotonin antagonists showed a serotonin-like lowering effect on the activation of factor XII and on the level of prekallikrein in plasma (BOL 148 1.0-4.0 mg/kg; methysergide 0.10-0.60 mg/kg; ergotamine 0.10-0.60 mg/kg). The results with the serotonin antagonist alone and in combination with dextran provided evidence that the serotonin-mediated part of the blood pressure fall can not be secondary to the effect of dextran on the plasma parameters assayed.

Anaphylaxis↗

Tolfenamic acid in acute and prophylactic treatment of migraine: a review.

The possible role of prostaglandins (PGs) in migraine has been the subject of increasing attention after the rather dramatic experiments done in man by Bergström and coworkers more than 25 years ago (1965). The role of PGs in migraine, however, is still hypothetical and not yet explained. PGs are known to sensitize nociceptors and produce hyperalgesia. PGs are involved in platelet aggregation thereby releasing serotonin. Vasodilatation, oedema and hyperalgesia in migraine have much in common with an inflammatory reaction. Tolfenamic acid (TA) inhibits PG biosynthesis and action and has an anti-aggregatory effect. TA is better than aspirin and as effective as ergotamine in treatment of acute migraine attacks. TA has fewer side effects than ergotamine. TA is as effective as propranolol in prophylactic treatment of migraine. The dose regimen of TA in acute treatment of migraine is 200 mg when the first symptoms of migraine appear. The treatment can be repeated after 2-3 hours if satisfactory effect is not obtained. The dose regimen of TA in prophylactic treatment of migraine is one sustained release tablet of 300 mg or 100 mg 3 times daily. After a treatment period of three months the regimen should be re-evaluated.

Acute Disease↗

Lysine-acetylsalicylic acid in acute migraine attacks.

Vasoconstrictive agents have been widely used in the treatment of migraine. These types of drugs have various side effects and are not suitable for many patients. Due to nausea or vomiting, nonoral treatment is often required, but only a few nonvasoconstrictive drugs exist in a parenteral form and are suitable for the treatment of acute migraine in the emergency setting. In a randomized, double-blind, crossover trial we evaluated the efficacy of 1,000 mg lysine-acetylsalicylic acid i.v. (LAS) compared to 0.5 mg ergotamine s.c. in 56 patients (112 attacks) with acute migraine. To gain further insight into the possible role of vasoconstriction, blood flow velocities (BFV) were measured in intra- and extracranial arteries using duplex sonography and transcranial Doppler sonography. Both agents were equally potent in relieving headache. Intravenous LAS resulted in a significantly faster relief and had fewer side effects. LAS had no effect on BFV. Ergotamine increased BFV in the middle cerebral artery only. No correlation was found between changes in BFV and the relief of headache. This is the first trial to compare the intravenous formulation of LAS in the treatment of migraine with another antimigraine medication and suggests that it is an effective and safe drug for the parenteral treatment of acute migraine attacks.

Acute Disease↗

Interaction of ergot alkaloids with dopaminergic receptors in the rat striatum and nucleus accumbens.

Various ergot alkaloids and derivatives were investigated for their interaction with dopaminergic receptors at the level of the rat corpus striatum and nucleus accumbens. Dihydro(DH)-ergotoxine, DH-ergocornine, DH-ergocryptine, DH-ergocristine, 2-Br-alpha-ergocryptine, ergotamine and DH-ergotamine were shown to inhibit, at micromolar concentrations, the dopamine-stimulated adenylate cyclase activity of rat striatal and nucleus accumbens homogenates. Interestingly, the inhibitory effect of the ergot drugs was higher in the nucleus accumbens than in the striatum. Moreover, the ergot drugs were more active in displacing 3H-haloperidol than 3H-dopamine from striatal membranes. The results, which are in apparent contradiction with previously obtained behavioral, pharmacological and clinical data, are discussed in the light of the possible presence in the central nervous system of distinct dopaminergic receptors with different conformations.

Adenylyl Cyclases↗