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PubMed1995

Differentiation between partial and silent 5-HT1D beta receptor antagonists using rat C6-glial and Chinese hamster ovary cell lines permanently transfected with a cloned human 5-HT1D beta receptor gene.

Intrinsic activities of serotonin (5-HT) receptor ligands at cloned human 5-HT1D beta receptor sites were determined by measuring cAMP responses in two permanently transfected cell types: rat C6-glial and Chinese hamster ovary (CHO)-K1 cells. Both transfected cell lines expressed a similar 5-HT1D beta receptor density (361 to 448 fmol/mg protein) and displayed a number of similar cAMP responses: marked inhibition of forskolin-stimulated cAMP formation by 5-HT; a similar agonist potency and efficacy with 5-carboxamidotryptamine (5-CT), 5-methoxytryptamine, bufotenine, sumatriptan, 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrolo-(1,2-a)quinoxal ine (CGS 12066B), 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)1H-indole (RU 24,969), and tryptamine, their maximal effect being comparable to that of 5-HT; less agonist efficacy with m-trifluoro-phenyl-piperazine (TFMPP) (it inhibited at most 63% of stimulated cAMP formation); and antagonist activity against the 5-CT-mediated agonist response with methiothepin, 2'-methyl-4-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxylic acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide (GR 127,935), and ritanserin. Metergoline and 1-naphtylpiperazine showed different intrinsic activities. In contrast to their pronounced antagonist activity in the transfected CHO-K1 cell line, the antagonist effect was only partial and absent for metergoline and 1-naphtylpiperazine in the transfected C6-glial cell line, respectively. In conclusion, these cell lines are useful as a tool to measure with high sensitivity differences in intrinsic activities of 5-HT receptor ligands and, therefore, discriminate between silent antagonists (no intrinsic activity) and antagonists with intrinsic activity (i.e. partial agonists), even though this intrinsic activity may be relatively weak.

Animals↗
PubMed1991

Vasodilatation elicited by 5-HT1A receptor agonists in constant-pressure-perfused rat kidney is mediated by blockade of alpha 1A-adrenoceptors.

The vasodilator mechanism of the putative serotonin1A (5-HT) receptor agonists, urapidil, 5-methyl-urapidil, ipsapirone, flesinoxan and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was investigated in constant-pressure perfused rat kidneys. The compounds (10(-12)-10(-7) mol bolus injection) neither enhanced basal flow nor evoked vasodilatation in kidneys preconstricted by 27 mM KCl, 1.5 mM BaCl2 or 10(-6) M prostaglandin (PG)F2 alpha, but evoked a dose-dependent, reversible and spiroxatrine-resistant increase in vasodilatation of organs preconstricted by 6 x 10(-7) M noradrenaline. 5-Carboxamidotryptamine and sumatriptan did not reverse the vasoconstriction induced by all stimuli or that induced by noradrenaline in the presence of 5-HT2 plus 5-HT3 receptor blockade. No correlation for the vasorelaxant drugs was found between their -log ED50 in rat kidney and pKi values at 5-HT1A binding sites in pig cortex as determined in radioligand experiments. The relaxation in rat kidney induced by 5-HT1A receptor agonists and alpha 1A-adrenoceptor-selective antagonists (WB 4101 and (+)-niguldipine) was significantly correlated with pKi values at alpha 1A binding sites in rat cortex and the pA2 values derived from contraction studies for competitive antagonism at alpha 1-adrenoceptors in prostatic portions of the rat vas deferens, but differed from pKi values for alpha 1B binding sites in rat cortex. Thus, the vasodilator effect of the 5-HT1A receptor agonists urapidil, 5-methyl-urapidil, ipsapirone, flesinoxan and 8-OH-DPAT in the noradrenaline-perfused rat kidney appears to be mediated by their concomitant alpha 1A-adrenoceptor blockade. No evidence for a vasodilator effect mediated through 5-HT1A receptors was found under our experimental conditions.

Adrenergic alpha-Antagonists↗
PubMed1991

Identification of putative 5-HT4 receptors in guinea-pig ascending colon.

Experiments were carried out to characterise pharmacologically a neuronal, non-5-HT3, 5-hydroxytryptamine (5-HT) receptor in guinea-pig isolated ascending colon. In preparations pretreated with methysergide (1 microM) and ondansetron (10 microM), 5-HT (0.003-1 microM) produced repeatable concentration-related contractions of guinea-pig ascending colon with an EC50 value of 29 (20-41) nM. The responses to 5-HT could be antagonised substantially by tetrodotoxin (0.3 microM) and atropine (1 microM) indicating a neuronal cholinergically mediated effect. The 5-HT-induced response was mimicked by 5-methoxytryptamine and alpha-methyl-5-HT with equipotent concentration ratios of 26 and 28, respectively. In contrast, 2-methyl-5-HT, 8-OH-DPAT, sumatriptan, phenylbiguanide and 5-hydroxyindalpine had no agonist activity up to 10 microM. The benzamides, metoclopramide, cisapride, R,S-zacopride and renzapride, mimicked the contractile action of 5-HT, acting like partial agonists. ICS205-930 (3 microM) acted as a competitive antagonist against 5-HT and 5-methoxytryptamine with estimated pKB values of 6.4 and 6.7 respectively. ICS205-930 (1 microM) also antagonised responses to R,S-zacopride and renzapride. Ketanserin (1 microM), phenylbiguanide (10 microM) and sulpiride (1 microM) had no effect on responses to 5-HT. We conclude that the pharmacological characteristics of the receptor, which mediates contraction of guinea-pig ascending colon by activation of cholinergic nerves, are consistent with it being of the putative 5-HT4 receptor type.

Animals↗
PubMed1992

Investigation into the 5-hydroxytryptamine-induced relaxation of the circular smooth muscle of guinea-pig stomach fundus.

The 5-HT receptor that mediates relaxation of circular muscle strips of the guinea-pig stomach fundus under resting tone was investigated. Concentration-dependent relaxation was obtained in the presence of atropine (0.2 microM) with 5-hydroxytryptamine (5-HT) (apparent mean pEC50 value, 5.27), 5-carboxamidotryptamine (7.35), 5-methoxytryptamine (4.98) and 5-methyltryptamine (4.58). 1-(m-Trifluoromethyl-phenyl)piperazine and 8-hydroxy-2-(di-n- propylamino)tetralin acted as partial agonists while 2-methyl-5-hydroxytryptamine, alpha-methyl-5-hydroxytryptamine, sumatriptan, metoclopramide and cisapride had little or no effect on the guinea-pig stomach fundus. The concentration-response curve for 5-HT was not affected by tetrodotoxin (0.3 microM), guanethidine (5 microM) or indomethacin (2 microM), suggesting that the relaxation is non-neuronal in origin and is independent of the release of catecholamines or prostanoids. The non-selective 5-HT receptor antagonist, metitepine (0.03-0.1 microM), the 5-HT1C/5-HT2 receptor antagonists, mianserin (0.3-1 microM), pizotifen (0.3-1 microM), ketanserin (3-10 microM), and the 5-HT1A/5-HT2 receptor antagonist, spiperone (3 microM), shifted the concentration-response curves for 5-HT to the right. A 5-HT3 receptor antagonist, ICS205-930 (1 microM), propranolol (1 microM) and phentolamine (1 microM) failed to block the 5-HT-induced relaxation. In conclusion, the results found with agonists and antagonists are compatible with the view that a 5-HT1-like receptor is involved in 5-HT-induced direct relaxation of circular muscle of guinea-pig stomach fundus.

Animals↗
PubMed1993

5-HT1 receptors mediating contraction in bovine cerebral arteries: a model for human cerebrovascular '5-HT1D beta' receptors.

We report on the pharmacological profile of the 5-HT receptor which induces contraction of the bovine isolated cerebral arteries. Several 5-HT receptor agonists were tested for their ability to induce vasoconstriction in bovine pial arteries and their potencies were compared to that of 5-HT. The rank order of agonist potency can be summarized as 5-carboxamidotryptamine (5-CT) = RU 24969 > or = 5-HT > sumatriptan > alpha-methyl-5-HT > methysergide > 2-methyl-5-HT > ((+-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene (8-OH-DPAT). Only methysergide induced a contraction which was smaller than that elicited by 5-HT. Antagonists with selective affinity at 5-HT1A/1B (propranolol), 5-HT1C (mesulergine), 5-HT2 (ketanserin, mianserin) and 5-HT3 (MDL 72222) sites were inactive to block the 5-HT-induced contraction. In contrast, the 5-HT1/5-HT2 receptor antagonists methiothepin and metergoline inhibited the 5-HT-induced response with relatively high affinity (pA2 = 8.16 +/- 0.26 and 6.73 +/- 0.05, respectively). Overall, this pharmacological profile indicated clearly that a 5-HT1 receptor, most closely related to the 5-HT1D subtype, is responsible for the 5-HT-induced contraction of bovine cerebral arteries. Correlation analysis of the potencies of a series of 5-HT receptor agonists and antagonists in bovine and human cerebrovascular preparations showed a highly significant positive correlation (r = 0.94, P = 0.0051).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The modulation of the increase in rat facial skin blood flow observed after trigeminal ganglion stimulation.

Electrical stimulation of the trigeminal ganglion causes an increase in facial skin blood flow in the anaesthetised rat, as measured by laser Doppler flowmetry. We investigated the modulation of this neurogenic vasodilator response using selective receptor agonists for putative prejunctional inhibitory receptors, as well as other pharmacological agents to further characterise this response. [D-Ala2,Me-Phe4,Gly5-ol]enkephalin (DAGO, a mu-opioid receptor agonist) inhibited the vasodilator response in a dose-related (0.058-5.8 mumol/kg i.v.) and naloxone-sensitive manner. A similar inhibitory response was observed with the local anaesthetic lignocaine (2% w/v, s.c. 20 microliters). In contrast, the histamine H3-receptor agonist alpha-methylhistamine (15 or 35 mumol/kg, i.v.) and the 5-HT1D receptor agonists sumatriptan (0.24 or 2.4 mumol/kg, i.v.) and CP 122,288 (0.0003-3 mumol/kg, i.v.) had no effect on these responses. Similarly, atropine (1.5 mumol/kg, i.v.) and indomethacin (28 mumol/kg, i.v.) did not alter the vasodilatation observed in this model. In conclusion, only mu-opioid receptor activation and local anaesthetic had any inhibitory action on the neurogenic vasodilatation observed in this model.

Animals↗
PubMed1996

Characterisation of a postjunctional 5-ht7-like and a prejunctional 5-HT3 receptor mediating contraction of rat isolated jejunum.

The 5-HT (5-hydroxytryptamine)-induced contractile biphasic concentration-effect curve in rat isolated jejunum was investigated. The pEC50 values for the first and second phases were 8.0 and 6.1, respectively. The responses were insensitive to atropine (0.1 microM), ketanserin (2 microM), (-)-pindolol (5 microM), yohimbine (0.1 microM) and GR 113808 ({1-[2-(methyl-sulphonylamino)ethyl]-4-piperidinyl}methyl 1-methyl-1 H-indole-3-carboxylate, 1 microM) but susceptible to cocaine (10 microM). The low affinity phase was blocked by tetrodotoxin (1 microM), ondansetron (1 microM) and SR48968 (S)-N-methyl-N-[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl]benzamide, 0.1 microM). The high affinity phase was antagonised non-surmountably by fluoxetine (1 microM) methysergide (0.1 microM), spiperone (0.1 microM) and methiothepin (0.1 microM). Ritanserin (0.01-0.1 microM) and mesulergine (0.01-0.1 microM) acted as surmountable, competitive antagonists with pA2 values of 8.0 and 8.1, respectively. Clozapine (0.1 microM) was a surmountable antagonist with an apparent pA2 value of 8.0. The rank potency order of the 5-HT receptor agonists was 5-CT (5-carboxyamidotryptamine) > or = 5-HT = 5-methoxytryptamine > or = alpha-methyl-5-HT > > 8-OH-DPAT ((+/-)-2-dipropyl-amino-8-hydroxy-1,2,3, 4-tetrahydronaphthalene) > dipropyl-5-CT > renzapride = sumatriptan. The responses to 5-HT and 5-CT were not potentiated by pargyline (10 and 100 microM). It is suggested that rat jejunum contains a neuronal 5-HT3 receptor facilitating neurokinin release and a contractile smooth muscle 5-HT receptor with a pharmacological operational profile similar to the cloned 5-ht7 receptor.

Animals↗
PubMed1995

Cloning and characterisation of the rabbit 5-HT1D alpha and 5-HT1D beta receptors.

The genes encoding the rabbit 5HT1D alpha and 5HT1D beta receptors have been cloned. The deduced amino acid sequence of these receptors shows 91-92% amino acid sequence identity with their human homologues, and similar high sequence identity with homologues from other species. The receptors were transiently expressed in COS-7 cells and exhibit a pharmacological profile closely resembling their human homologues, including a higher affinity of ketanserin for the 5-HT1D alpha subtype. However, sumatriptan had a lower affinity for both the rabbit receptors compared to their human counterparts. This may be accounted for by differences between the primary amino acid sequences of these species homologues.

Amino Acid Sequence↗
PubMed1993

Receptors implicated in the actions of serotonin on chicken ileum longitudinal smooth muscle.

The presence of serotonin (5-HT) in the chicken gastrointestinal tract has been previously reported, but its motor effects have been poorly described. The aims of this work were: A) to define the effects of 5-HT on chicken longitudinal ileum; B) to explore the mechanisms by which such effects occur and C) to identify the subtype(s) of 5-HT-ergic receptors implicated. The motor responses to 5-HT were assayed in vitro using ileal strips taken from male White Leghorn chickens 7-9 week old. 5-HT elicited ileal contraction (EC50 9.6 x 10(-8) M), which was markedly decreased in the presence of tetrodotoxin (TTX). Repeated exposure of the tissue to supramaximal concentrations of 5-HT did not however lead to desensitization. Atropine (10(-6) M), ketanserin (10(-5) M), methysergide (10(-5) M) and methiothepine (10(-6) M) attenuated the response to 5-HT. Ketanserin was an effective inhibitor of the residual response to 5-HT obtained even in the presence of TTX. Several serotonergic agonists were assayed to further analyse the type of receptors involved in the response to 5-HT. 5-methoxytryptamine (5-MOT), a mixed 5-HT1, 5-HT2 and 5-HT4 agonist, reproduced all the effects of 5-HT. 8-OH-DPAT, a selective 5-HT1A agonist, trifluoromethylphenylpiperazine, a mixed 5-HT1B/C agonist, and m-chlorophenylbiguanide, a 5-HT3 agonist, did not induce any consistent contractile effects. Sumatriptan, a 5-HT1D agonist, exerted a slight agonistic effect which was blocked by methiothepine and decreased by TTX but not by atropine. Cisapride, a 5-HT4 partial agonist in mammals, decreased the effects of both 5-HT and 5-MOT. These results indicate that chicken ileum contains 5-HT1 receptors similar to the 5-HT1D mammalian subtype but not the 5-HT1A, 5-HT1B, 5-HT1C or 5-HT3 subtypes. 5-HT2 receptors are also present and would appear to be located on smooth muscle.

Animals↗
PubMedDate not supplied

Primary care for women. Assessment and management of headache.

Headache is the seventh leading presenting complaint for ambulatory care encounters in the United States, which accounts for 18.3 million, or 43.2 per 1000, outpatient visits per year. Headache disorders have historically been difficult to tract and study. This problem has been greatly ameliorated since the development, in 1988, of the international headache classification of the International Headache Society. Tension-type headache and migraine headache predominantly affect women, whereas cluster headache predominantly affects men. Advances both in diagnosis and in treatment modalities such as prophylactic treatments, stress reduction and biofeedback, and the use of sumatriptan, have helped to make the management of headache appropriate for nurse-midwives in the primary care setting.

Cluster Headache↗
PubMed1995

Innervation of cerebral arteries by nerves containing 5-hydroxytryptamine and noradrenaline.

Noradrenaline (NA)-containing nerves, mainly originating in the sympathetic superior cervical ganglia, supply large and small cerebral arteries. In large cerebral arteries, nerves containing serotonin (5-hydroxytryptamine, 5-HT) may represent neuronal uptake of circulating 5-HT by sympathetic nerves. 5-HT-containing nerves supplying small pial vessels probably have a central origin in the dorsal raphe nucleus. In most species, NA is a weak vasoconstrictor (alpha 1- or alpha 2-adrenoceptors), while 5-HT is a potent vasoconstrictor (5-HT2 or 5-HT1-like receptors) of large cerebral arteries. In contrast, both NA and 5-HT tend to cause vasodilatation in small pial vessels and arterioles. Adrenergic and serotonergic transmission can be modulated by pH, a range of putative neurotransmitters and neuromodulators, and by the endothelium. Sumatriptan, a 5-HT1-like receptor agonist, has been shown to be effective in the treatment of migraine. Changes in NA- or 5-HT-containing nerves and/or in the responses of cerebral vessels to NA and 5-HT have been observed in a variety of vascular disorders, including cerebral vasospasm following subarachnoid haemorrhage, hypertension, and atherosclerosis.

Animals↗
PubMed1992

A subfamily of 5-HT1D receptor genes.

The recent discovery and characterization of three new 5-HT1 receptor clones and the pharmacological characterization of one orphan receptor (dog RDC4) has revealed a surprising complexity within the 5-HT1D receptor subfamily. This receptor subfamily, which is believed to be the target of the anti-migraine drug sumatriptan and may regulate feeding behavior, anxiety, depression, cardiac function and movement, can now be approached on a molecular level. These cloning discoveries have also taught us an important general lesson about the molecular pharmacology of G protein-coupled receptor genes: species homologues of a gene (the equivalent gene in different species) may be highly homologous in amino acid sequence yet display very different pharmacological properties. Conversely, two different genes in the same species (intraspecies subtypes) that display only moderate degrees of transmembrane amino acid homology can display nearly indistinguishable pharmacological properties. In discussing the implications of these findings for both 5-HT receptors and G protein-linked receptors in general, Paul Hartig, Theresa Branchek and Richard Weinshank approach the question: why have so many receptor subtypes been preserved in the genome? In addition, controversy has been raging for several years over the classification of 5-HT1B receptors (found only in rat brain) and 5-HT1D receptors. Were they different subtypes or simply species homologues of the same receptor? Recent cloning studies have apparently complicated this issue, but the answer to the question is, in fact, becoming clearer.

Amino Acid Sequence↗
PubMed1996

GR127935: a potent and selective 5-HT1D receptor antagonist.

GR127935 is the most potent 5-HT1D receptor antagonist yet described, possessing nanomolar affinity at human 5-HT1D receptors. Sumatriptan-induced contractions of the dog isolated basilar artery and saphenous vein are antagonised by GR127935 in an insurmountable manner indicative of its slow dissociation from the 5-HT1D receptor. 5-HT1D receptor-mediated hypothermia and rotational behaviour in guinea-pigs are antagonised potently, and with long duration, by GR127935, administered by a variety of routes. GR127935 also blocks central 5-HT1D autoreceptors in vitro and in vivo. GR127935 has much lower affinity at other 5-HT, and non-5-HT, receptors. In functional studies, GR127935 fails to affect 5-HT2 receptor-mediated 'wet dog shakes' in guinea-pigs and 5-HT1A receptor-mediated inhibition of 5-HT release in rat dorsal raphé nucleus. The compound has a good safety profile in all species tested. It is concluded that GR127935 is a useful pharmacological tool to characterise 5-HT1D receptor function.

Animals↗
PubMed1996

Role of endothelin in mediating neurogenic plasma extravasation in rat dura mater.

In addition to their potent vasoconstrictor properties, the endothelins (endothelin-1 and -3) may possess neurotransmitter/neuromediator and neuroendocrine actions. The aim of the present study was to evaluate the role of endothelins (ET) in mediating neurogenic inflammation of cephalic tissues in the rat. For this purpose, bosentan, a specific non-peptide mixed antagonist of ET receptors, was tested in rat models of neurogenic and non-neurogenic plasma extravasation in the dura mater and extracranial tissues (eyelid, conjunctiva, lip, tongue). Bosentan was effective for preventing neurogenic inflammation in the dura mater induced by unilateral electrical stimulation of the trigeminal ganglion or intravenous injection of capsaicin, whereas it was ineffective in extracranial tissues or after injection of substance P (non-neurogenic inflammation). The effect of nerve fiber stimulation on ET plasma concentrations in superior sagittal sinus was measured using selective radioimmunoassays for ET-1 and -3. Endothelin-3 concentration significantly increased after intravenous injection of capsaicin, whereas ET-1 levels remained unchanged. Competition binding assays on microsomal membranes from the trigeminal ganglion revealed a single class of binding sites with equal affinity for ET-1 and ET-3, suggesting a homogenous population of ETB receptors. The role of ETB receptors in mediating inflammation was evidenced by the lack of efficacy of a selective ETA receptor antagonist, in contrast to the full efficacy of a selective ETB receptor antagonist, for preventing neurogenic inflammation induced by unilateral stimulation of the trigeminal ganglion. The role of ETB receptors was finally confirmed by the observation that exogenous administration of the ETB receptor agonist sarafotoxin S6c also induced plasma protein extravasation in the dura mater. This extravasation was not a direct effect of ETB receptor stimulation, because it was inhibited by spantide, a selective tachykinin receptor antagonist. These data strongly suggest that ET, acting through ETB receptors, may play an important role in mediating neurogenic inflammation in the meninges of rats. Since the profile of activity of bosentan is similar to that of the 5-HT1D/B agonists, sumatriptan and ergot alkaloids, one may speculate that ET receptor antagonists might be potentially effective in the treatment of acute migraine attacks.

Animals↗
PubMed1996

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?

Migraine is a common and debilitating condition. Its treatment has received considerable attention in recent times with the introduction into clinical use of the serotonin (5HT)1B/D-like agonist sumatriptan. It is known from human studies that the intracranial blood vessels and dura mater are important pain-sensitive structures since mechanical or electrical stimulation of these vessels, such as the superior sagittal sinus, causes pain. We have developed a model of craniovascular pain by stimulating the superior sagittal sinus and monitoring trigeminal neuronal activity using electrophysiological techniques. In this study we determined the effect of intravenous administration of the novel anti-migraine compound zolmitriptan (311C90) upon evoked neuronal activity in trigeminal neurons. Nine adult cats were anaesthetised with alpha-chloralose (60 mg/kg, i.p.; 20 mg/kg, i.v., 2-hourly) with all surgery being conducted under halothane (1-3%). The superior sagittal sinus was isolated for electrical stimulation. Recordings were made from caudal trigeminal neurons at the C2 level of the cervical spinal cord with tungsten-in-glass microelectrodes. Signals were amplified and analysed by a custom-written program that enabled software filtering and extraction of both evoked potential and single cell data. Data were collected before and after administration of zolmitriptan. Electrical stimulation of the superior sagittal sinus resulted in activation of neuronal elements within the trigeminal nucleus that could be monitored as single unit activity or as evoked potentials, the latter reflecting both primary afferent and trigeminal cell body activity. 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. Similarly, the probability of firing for trigeminal neurons was reduced from a control level of 0.63 +/- 0.1 to 0.13 +/- 0.05 after a dose of 100 micrograms/kg intravenously. These effects were dose-dependent and were significantly different from the effect of vehicle (P < 0.05). These data demonstrate that systemically administered zolmitriptan can inhibit evoked trigeminovascular activity within the trigeminal nucleus. This inhibition of trigeminal activity may play a role in the anti-migraine actions of this compound and offers the prospect of a third pathophysiologically consistent target site for anti-migraine drug effects.

Animals↗
PubMed1995

Characterization of 5-hydroxytryptamine receptors in goat cerebral arteries.

1. In isolated goat middle cerebral artery segments, 5-hydroxytryptamine (5-HT, 10(-8)-3 x 10(-5) M) elicited concentration-dependent contractions with EC50 = 2.1 (1.9-2.5) x 10(-7) M and Emax = 64 +/- 2% of 50 mM KCl-induced contraction. 2. Several 5-HT receptor agonists were used: (a) the agonist of 5-HT2 receptors alpha-methyl-5-hydroxy-tryptamine (10(-7)-3 x 10(-4) M) induced strong contraction (51 +/- 6%); (b) the selective agonists of 5-HT1 receptors sumatriptan (10(-8)-10(-5) M) and 5-carboxamidotryptamine (10(-9)-10(-4) M) and the agonist of 5-HT1A receptors 8-hydroxy-2-(di-n-propylamino)tetralin (10(-7)-3 x 10(-5) M) induced weak contractions (8, 18 and 14%, respectively); and (c) the agonist of 5HT3 receptors 2-methyl-5-hydroxytryptamine (3 x 10(-6)-10(-4) M) induced almost negligible contraction. 3. Pretreatment with the antagonist of 5-HT1A and 5-HT1B receptors cyanopindolol (10(-8), 10(-6) M), the antagonist of 5-HT1/5-HT2 receptors methysergide (10(-11), 10(-9) M) and the antagonist of 5-HT2 receptors ketanserin (10(-11), 10(-9) M) induced non-competitive inhibition of the concentration-response curve to 5-HT. The antagonist of 5-HT3 receptors 3-trophanyl-3,5-dichlorobenzoate (10(-7), 10(-5) M) did not inhibit the contractile curve to 5-HT. 4. These results suggest that 5-HT contracts the goat middle cerebral artery by acting mainly on 5-HT2 receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

The pharmacologic treatment of acute migraine headaches.

Pharmacologic agents useful in the treatment of acute migraine headaches include nonsteroidal antiinflammatory drugs (NSAIDs), ergotamines, and analgesics. Parenteral ergotamines, antiemetics, NSAIDs, corticosteroids, and sumatriptan can be successfully administered in the office or emergency room setting. In this article, evidence regarding the efficacy of these agents is reviewed.

Acute Disease↗
PubMed1993

Diagnosis and treatment of cluster headache.

Cluster headache (CH) is a rare form of headache occurring in both episodic and chronic forms. The painful attacks are short-lived, occur unilaterally, and are associated with signs and symptoms of autonomic involvement. Attacks frequently occur at night and can be precipitated by ingestion of alcohol. In the episodic form, attacks occur daily for some weeks followed by a period of remission. In the chronic form, attacks can continue for years. Inheritance is not a factor in CH. Treatment can be symptomatic or prophylactic. Agents used to treat individual attacks include inhalation of oxygen, rapidly acting forms of ergotamine and dihydroergotamine, and sumatriptan. Prophylactic treatment employs calcium-channel-blocking agents, methysergide, lithium, and corticosteroids. Surgical modalities, notably thermocoagulation of the gasserian ganglion, can provide relief in those who are resistant to medical management.

Acute Disease↗