8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition site

Middlemiss, Derek N.; Fozard, John R.

doi:10.1016/0014-2999(83)90230-3

Cited by 853 publications

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“…Binding sites displaying high or low affinity for spiperone have been designated as ~-H T~A and ~-H T~B , respectively. Ligands selective for the ~-H T~A (e.g., 8-hydroxy-2-(di-n-propylamino) tetralin or 8-OH-DPAT) and 5-HT1~ subtypes (e.g., RU 24969) have been identified (Middlemiss and Fozard, 1983;Sills et al, 1984). Competition experiments in which these compounds were tested for their ability to displace [3H]-5-HT binding revealed high densities of ~-H T~A sites in the septa1 nucleus, hippocampal formation, and dorsal raphe nucleus and high densities of ~-H T~B sites in the dorsal subiculum, globus pallidus, and substantia nigra (Marcinkiewicz et al, 1984;.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological responses of serotoninergic dorsal raphe neurons to 5‐HT_1A and 5‐HT_1B agonists

Sprouse¹,

Aghajanian²

1987

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A direct comparison was made of the effects of serotonin 5 -H T 1~ and 5-H T~B selective compounds on the spontaneous firing rate of dorsal raphe serotoninergic neurons in chloral-hydrate-anesthetized rats. Following intravenous administration, the ~-H T~A selective compounds ipsapirone (TVX Q 7821) and LY 165163 potently inhibited single-unit activity in a dose-dependent manner whereas the ~-H T~B selective compounds, m-chlorophenylpiperaine (mCPP) and trifluoromethylphenylpiperazine (TFMPP), displayed only weak or irregular actions. Low microiontophoretic currents of ipsapirone and LY 165163 were also effective in suppressing spontaneous firing; dose-response relationships for the ~-H T~A compounds were indistinguishable from that of 5-HT itself. In contrast, dorsal raphe neurons were only weakly responsive to microiontophoretic application of mCPP and TFMPP dose-response relationships for the ~-H T~B compounds were significantly displaced from that of 5-HT. In intracellular studies, ipsapirone and LY 165163, when added to the media bathing brain slices, mimicked the actions of 5-HT in hyperpolarizing dorsal raphe cell membranes and decreasing input resistance; however, the maximal effects of the 5-Efl"l'~ compounds on these membrane properties exceeded those of 5-HT. In summary, dorsal raphe 5-HT neurons appear highly responsive to 5-H T 1~, but not to ~-H T~B compounds; these findings are discussed with regard to the 5-HT receptor subtypes as candidates for the somatodendritic autoreceptor of dorsal raphe Ipsapirone, LY 165163, mCPP, TFMPP neurons.

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Section: Introductionmentioning

confidence: 99%

Electrophysiological responses of serotoninergic dorsal raphe neurons to 5‐HT_1A and 5‐HT_1B agonists

Sprouse¹,

Aghajanian²

1987

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827

335

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“…In addition certain 5-HT-receptor agonists have been found to bind selectively to either the 5-HTIA or 5-HTIB site. One such compound is 8-hydroxy-2-(n-dipropylamino) tetralin (8-OH-DPAT) which binds specifically to the 5-HTIA site (Middlemiss & Fozard, 1983). The piperidinyl indole derivative 5-methoxy-3- [1,2, 3,6-terahydro-4-pyridinyl]-1H indole (RU24969) has been proposed as a selective ligand for the 5-HTIB site (Sills et al, 1984;Doods et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

Involvement of 5‐HT_1A‐ and α₂‐receptors in the decreased 5‐hydroxytryptamine release and metabolism in rat suprachiasmatic nucleus after intravenous 8‐hydroxy‐2‐ (n‐dipropylamino) tetralin

Marsden

Martin

1986

British J Pharmacology

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1 The 5-hydroxytryptamine1A-receptor agonist 8-hydroxy-2-(n-dipropylamino) tetralin (8-OH-DPAT, 0.1 mg kg-' i.v.) decreased the height of the extracellular 5-hydroxyindoleacetic acid (5-HIAA) oxidation peak recorded in the suprachiasmatic nucleus (SCN) of the anaesthetized rat by use of differential pulse voltammetry. -2 The decrease in extracellular 5-HIAA produced by 8-OH-DPAT could be partially attenuated by prior administration of the non-selective 5-HT receptor antagonist methiothepin (1 mg kg-i.v.). The 5-HT2-receptor antagonist ritanserin (0.2 mg kg-' i.v.) did not appear to block the effects of 8-OH-DPAT.3 The selective ligand for 5-HTIA recognition sites TVX Q 7821 (isapirone, 1 mg kg-' i.v.) decreased the extracellular level of 5-HIAA in the SCN but to a lesser extent than 8-OH-DPAT. The response to 8-OH-DPAT was attenuated by prior administration of TVX Q 7821 to a level suggesting that TVX Q 7821 had blocked the effect of intravenous 8-OH-DPAT. 4 Idazoxan (0.2mg kg-i.v.) an X2-adrenoceptor antagonist, completely blocked the effect of 8-OH-DPAT on the 5-HIAA oxidation peak recorded in the SCN, whilst having no effect on the 5-HIAA oxidation peak when given alone. 5 At a dose of 0.5mg kg-' i.v. idazoxan induced a 120% increase in the height ofthe indole oxidation peak, suggesting that 5-HT release and metabolism in the rat SCN may be influenced by tonic adrenergic inputs. 6 The data in this paper suggest that 5-HTIA-and a2-receptors are involved in the effects of i.v. administered 8-OH-DPAT on 5-HT release and metabolism in the SCN in vivo.

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“…Receptors for 5-hydroxytryptamine (5-HT) were subdivided into 5-HT1 and 5-HT2 based on the affinities of radioligands for brain binding sites (see Peroutka & Snyder, 1979) and the 5-HT1 binding site has been further subclassified (Middlemiss & Fozard, 1983). In the periphery, 5-HT is a potent vasoconstrictor in many vascular beds, but the constriction seems to involve two distinct receptor subtypes: contractions to 5-HT in the rabbit aorta, rat aorta, rat tail artery and dog femoral artery are mediated by 5-HT2-receptors at which ketanserin is a potent and competitive antagonist (Humphrey, 1984;Peroutka, 1984); contractions in the dog saphenous vein and human and dog basilar arteries are mediated by 5-HT1 or 5-HTI-like receptors (Peroutka, 1984;Feniuk et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

An examination of 5‐hydroxytryptamine receptors in human saphenous vein

Docherty

Hyland

1986

British J Pharmacology

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1 We have examined the effects of antagonists on the isometric contraction of the human saphenous vein produced by 5-hydroxytryptamine (5-HT).2 The 5-HT2-antagonist ketanserin (1 gM) had little effect on the lower part of the concentrationresponse curve to 5-HT, but markedly shifted the upper part of the curve. 3 Yohimbine caused an approximately parallel shift of the concentration-response curve to 5-HT, with a pA2 of 5.48, much lower than its pA2 against noradrenaline in the absence (6.36) or presence (7.06) of cocaine. 4 It is concluded that there are two components to the contractile response to 5-HT in human saphenous vein: at low concentrations 5-HT activates a yohimbine-sensitive receptor, and at higher concentrations 5-HT activates a 5-HT2-receptor.

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8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition site

Cited by 853 publications

References 2 publications

Electrophysiological responses of serotoninergic dorsal raphe neurons to 5‐HT_1A and 5‐HT_1B agonists

Electrophysiological responses of serotoninergic dorsal raphe neurons to 5‐HT_1A and 5‐HT_1B agonists

Involvement of 5‐HT_1A‐ and α₂‐receptors in the decreased 5‐hydroxytryptamine release and metabolism in rat suprachiasmatic nucleus after intravenous 8‐hydroxy‐2‐ (n‐dipropylamino) tetralin

An examination of 5‐hydroxytryptamine receptors in human saphenous vein

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8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition site

Cited by 853 publications

References 2 publications

Electrophysiological responses of serotoninergic dorsal raphe neurons to 5‐HT1A and 5‐HT1B agonists

Electrophysiological responses of serotoninergic dorsal raphe neurons to 5‐HT1A and 5‐HT1B agonists

Involvement of 5‐HT1A‐ and α2‐receptors in the decreased 5‐hydroxytryptamine release and metabolism in rat suprachiasmatic nucleus after intravenous 8‐hydroxy‐2‐ (n‐dipropylamino) tetralin

An examination of 5‐hydroxytryptamine receptors in human saphenous vein

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Electrophysiological responses of serotoninergic dorsal raphe neurons to 5‐HT_1A and 5‐HT_1B agonists

Electrophysiological responses of serotoninergic dorsal raphe neurons to 5‐HT_1A and 5‐HT_1B agonists

Involvement of 5‐HT_1A‐ and α₂‐receptors in the decreased 5‐hydroxytryptamine release and metabolism in rat suprachiasmatic nucleus after intravenous 8‐hydroxy‐2‐ (n‐dipropylamino) tetralin