Disease relevance of zolmitriptan

• Patients treated a single moderate or severe migraine headache with 2.5 mg zolmitriptan or placebo and recorded clinical efficacy and adverse events on a diary form [1].
• CONCLUSION: Oral zolmitriptan is efficacious in episodic cluster headache [2].
• Photophobia and nausea also showed improvement after 311C90 [3].
• In a 6-hour rat model of pneumococcal meningitis, zolmitriptan and naratriptan reduced the influx of leukocytes into the cerebrospinal fluid, and attenuated the increase of regional cerebral blood flow [4].
• Other symptoms of migraine, including nausea, photophobia and phonophobia are also alleviated with zolmitriptan [5].

Psychiatry related information on zolmitriptan

• RESULTS: The growth hormone response to zolmitriptan was blunted in patients with a melancholic depressive syndrome [6].
• The results demonstrate that therapeutic doses of zolmitriptan are unlikely to cause clinically significant impairment in psychometric performance [7].
• Zolmitriptan doses less than 20 mg had no statistically significant effects on choice reaction time, the Stroop test, visual analog scale (VAS) assessments of physical sedation, tranquilization and other types of feelings, the logical reasoning test or the adaptive tracking test [7].
• Lack of an effect of zolmitriptan (Zomig, 311C90) on psychometric task performance: results of a placebo-controlled study in healthy volunteers [7].
• Zolmitriptan (a 5-HT1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder [8].

High impact information on zolmitriptan

• METHODS: The authors compared the efficacy of two doses of ketoprofen (75 or 150 mg) with that of placebo (primary analysis) and zolmitriptan 2.5 mg (secondary analysis) on one to four consecutive attacks in 235 intent-to-treat patients (out of 257 randomized patients) with migraine with or without aura [9].
• With ultrasonography and applanation tonometry used 1.5 hours after the oral intake of sumatriptan (50 mg), rizatriptan (10 mg), zolmitriptan (2.5 mg), or placebo arterial vessel wall properties, blood flow and pressure waveforms were measured in common carotid, brachial, and temporal arteries [10].
• Isobaric compliance of the brachial artery, 0.077 +/- 0.010 mm2/kPa after placebo, decreased (P < .01) by 11% +/- 8%, 11% +/- 11%, and 23% +/- 7% after administration of sumatriptan, rizatriptan, and zolmitriptan, respectively [10].
• For all other secondary endpoints, zolmitriptan 10 mg was significantly superior to placebo in episodic cluster headache patients, whereas zolmitriptan 5 mg was significantly superior to placebo for three of the four secondary endpoints [2].
• In this study we investigated the cardiovascular and central nervous system effects and the pharmacokinetics of zolmitriptan in young and elderly adults [11].

Chemical compound and disease context of zolmitriptan

• 311C90 (Zomig; zolmitriptan) is a novel, selective serotonin (5HT)1B/1D receptor agonist with both central and peripheral activity, now in late-stage clinical development for acute oral treatment of migraine [12].
• In one of them, sumatriptan or zolmitriptan was administered in vivo subcutaneously (s.c.) in a dose of 0.1 mg per kg body weight [13].
• Comparison of rizatriptan 10 mg vs. zolmitriptan 2.5 mg in the acute treatment of migraine. Rizatriptan-Zolmitriptan Study Group [14].
• In a multicentre double-blind, double-dummy, parallel-groups trial, 1587 outpatients with migraine by IHS criteria were randomised in a 3: 3 : 3: 1 ratio to eletriptan 80 mg, eletriptan 40 mg, zolmitriptan 2.5 mg or placebo [15].
• In 20 healthy subjects without migraine and in 20 healthy subjects with migraine without aura, platelet and erythrocyte aggregation were measured before and after intake of placebo, acetylsalicylic acid, ergotamine tartrate, zolmitriptan and sumatriptan [16].

Biological context of zolmitriptan

• In the elderly, mean peak supine systolic blood pressure values were 9 to 16 mm Hg higher after zolmitriptan than after placebo [11].
• Blood pressure, heart rate, ECG, and central nervous system effects were monitored, and pharmacokinetic parameters of zolmitriptan and its metabolites calculated [11].
• The evoked potential recorded from the trigeminal nucleus was 207 +/- 14 microV and was reduced by zolmitriptan (100 micrograms/kg, i.v.) to a mean of 98 +/- 17 microV [17].
• The efficacy of zolmitriptan appears to be maintained, with no tachyphylaxis, following repeated administration for multiple attacks of migraine over a prolonged period of time, with high headache response rates reported over all attacks [5].
• The most common adverse events with zolmitriptan therapy are asthenia, heaviness other than that of the chest or neck, dry mouth, nausea, dizziness, somnolence, paraesthesia, warm sensation, tightness, vasodilation and chest pain [5].

Anatomical context of zolmitriptan

• We conclude that zolmitriptan acts centrally by reducing the inhibition within the motor cortex [18].
• The results suggest that the action of zolmitriptan on motor cortical excitability does not result from changes at the level of the cell membrane but from the influence on GABAergic inhibitory interneurons [18].
• These data demonstrate that systemically administered zolmitriptan can inhibit evoked trigeminovascular activity within the trigeminal nucleus [17].
• Inhibition of trigeminal neurons by intravenous administration of the serotonin (5HT)1B/D receptor agonist zolmitriptan (311C90): are brain stem sites therapeutic target in migraine [17]?
• Zolmitriptan crosses the intact blood-brain barrier to inhibit trigeminovascular activation in the brainstem [19].

Associations of zolmitriptan with other chemical compounds

• Anpirtoline, like other 5-HT1B agonists (CP-94,253, zolmitriptan), decreased both instigated and frustration-heightened aggression, while motor behavior was unaffected [20].
• Naratriptan tended to increase ASF slope (mean difference 0.23 +/- 0.62 microV/10 dB, p = 0.06) while zolmitriptan (0.08 +/- 0.95 microV/10 dB, p = 0.35) did not [21].
• In membranes obtained from cells co-expressing the porcine 5-HT(1B) receptor and a mutant G(alphao)Cys(351)Ile protein, 5-HT and zolmitriptan increased, while the 5-HT(1B) receptor antagonist SB224289 decreased basal [(35)S]-GTPgammaS binding, thus showing inverse agonism [22].
• Thirty healthy subjects received either ASA or ZOL vs. placebo using a double blind cross over design. nBR was recorded in all patients and subjects before, 60 and 90 min after treatment [23].
• There was a significant increase in serum growth hormone after zolmitriptan compared to placebo, however there were no significant effects on cortisol, prolactin or oral temperature [24].

Gene context of zolmitriptan

• 4. Primary metabolism of zolmitriptan is dependent mainly on CYP1A2, whereas MAO-A is responsible for further metabolism of N-desmethyl-zolmitriptan, the active metabolite [25].
• 6. These results show that 311C90, a novel member of the 5-HT1B/1D agonist drug class, exhibits a high degree of pharmacological specificity [26].
• Zolmitriptan-induced growth hormone release in humans: mediation by 5-HT1D receptors [27]?
• This suggests that MAO-A is involved in the metabolism of 183C91 and it may be prudent to limit the daily zolmitriptan dose in migraine patients maintained on a MAO-A inhibitor [28].
• The latency of the P300 ERP was unaffected by zolmitriptan and there was no clinically significant effect on the EEG [29].

Analytical, diagnostic and therapeutic context of zolmitriptan

• Oral administration of zolmitriptan, a novel 5-hydroxytriptamine receptor agonist, to eight healthy volunteers significantly reduced motor cortical excitability as tested by paired transcranial magnetic stimulation (TMS) at short interstimulus intervals [18].
• Effectiveness of Intranasal Zolmitriptan in Acute Cluster Headache: A Randomized, Placebo-Controlled, Double-blind Crossover Study [30].
• AIMS: The aim of the study was to use the 5-HT(1D) receptor agonist, zolmitriptan, to test the sensitivity of 5-HT(1D) receptors in patients with depression before and after treatment with selective serotonin reuptake inhibitors (SSRIs) [6].
• The purpose of this article is to review data available from pharmacological and clinical trials with zolmitriptan and to summarize the clinically relevant features that distinguish this agent [31].
• Plasma concentrations of zolmitriptan and a 17-lead quantitative EEG were assessed at the same timepoints [29].

References