Anti-migraine

Interest in this receptor has been generated by the possibility that its activation accounts for the anti-migraine effects of the non-selective 5-HTib/id agonist, sumatriptan. The exact process(es) that account for this action are unresolved but... 

Anti-malarials Anti-migraine agents Anti-muscarinic agents... 

Sumatriptan was specifically developed as an anti-migraine drug. Injectable sumatriptan has been shown to be more effective than injectable DHE at two hours but the rate of recurrence (30 0%) is higher than with DHE. Efficacy is better and delay to action is shorter with the injectable formulation. Both the nasal spray and the injectable formulation... 

Buzzi, M. G. and Moskowitz, M. A. The anti-migraine drug sumatriptan (GR 43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater, Br. J. Pharmacol. 1990, 99, 202-206. 

Simulation Simulations exploring the effect of the rate of absorption, bioavailability after an extravascular administration, and the rate of activation/inactivation of the anti-migraine effect were performed. To achieve a response rate of 60% at 2 h, the rate of absorption seems to play a minor role if bioavailability fractions of at least 0.2-0.3 can be achieved and kon is >0.081 ml/ng. At later times after administration, higher values of A0ff are associated with faster offset of the response. 

The synthesis of the Bristol-Myers Squibb anti-migraine drug Avitriptan (a 5-HT1D receptor antagonist) involves this palladium-catalysed indole synthesis. Suggest a mechanism and comment on the regioselectivity of the alkyne attachment. 

HT1 -R agonist (aA-R blocker) [anti-migraine as vasoconstrictor, selective venoconstrictive]... 

Inhibits prolactin release (D2-R agonist) [anti-migraine, ergotism, haemostatic, vasoconstrictor]... 

Amery, W.K., Wauquier, A., Van Neuten, J.M. (1981). The anti-migrainous pharmacology of flunarizine (R14950), a calcium antagonist. Drugs Exp. Clin. Res. 7 1-10. 

Continued use of some anti-migraine drugs can lead to rebound headache, marked by frequent or chronic headaches, especially in the early morning hours. Rebound headache is avoided by using anti-migraine drugs under a doctor s supervision, with the minimum dose necessary to treat symptoms. Patients with frequent migraines may need preventive therapy. 

Rolan P. Potential drug interactions with the novel anti-migraine compound zolmitriptan (Zomig, 311C90). Cephalalgia 1997 17(Suppl 18) 21-7. 

We are all aware of the substantial benefits patients have derived from the use of botanical derivatives to treat medical conditions (digitalis comes to mind immediately). The clinical results with feverfew, which has benefits as an anti-migraine agent, is but one example [4]. However, the acceptability of these plant extracts arose only after safety and efficacy was assured. An example is research conducted by the Chinese on... 

Glen, R. C., Martin, G. R., Hill, A. R, Hyde, R. M., Woollard, P. M., Salmon, J. A., Buckingham, J., Robertson, A. D. Computer-aided design and synthesis of 5-substimted tryptamines and their pharmacology at the 5-HTlD receptor discovery of compounds with potential anti-migraine properties. J. Med. Cherru 1995,5S(18), 3566-3580. 

Three chemical steps convert cyclohexane-1,4-dione into a compound which is used for the synthesis of the anti-migraine drug frovatriptan. Suggest how this transformation is carried out. 

Acid maleate, CnH Oj, Cuvafir, Dopergin, Eunal, Lysenyl. Prisms from ethanol, mp 200 (dec). [a]f,° +288" (c = 0.5 in methanol), uv max (methanol) 313 nm. LDVI i.v in mice 14.4 mg/kg (Votava, Lamplova). therap cat Anti migraine prolactin inhibitor. 

Perhaps the most prominent example with respect to anti-secretive effects of STLs is related to the well-known anti migraine activity of feverfew (Tanacetum parthenium, Asteraceae). The main STL from this plant is parthenolide (PAR), structure 1 in Fig. (15), and it has been shown that PAR is a potent inhibitor of serotonin (5HT)-release from thrombocytes. Although it is not finally clarified to which extent this effect is involved along with the numerous other reported activities of PAR in the clinically proven efficacy of feverfew [71, 72], it should at least contribute to the overall effect. 

Hamel et al. [53] carried out northern blot hybridisation studies and demonstrated the presence of 5-HTn3 mRNA in bovine caudate nucleus and cerebral cortex, and in human cerebral cortex. 5-HTjo receptor hybridisation was not observed with RNA extracts from pial vessels in either species. Hybridisation with the 5-HTidp receptor probe revealed the presence of mRNA transcripts in both human smd bovine cerebral tissue and pial vessels. This work indicating the presence of 5-HT,Dp, but not 5-HTip , receptor mRNA in bovine and human cerebral arteries located outside the brain parenchyma, but neither type in intraparenchymed microvessels or capillaries suggests that the anti-migraine effects seen with sumatriptan, if vascular related, are probably mediated via 5-HTii, receptors. 

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