Resolution and absolute configuration of an ergoline-related dopamine agonist, trans-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H(or 2H)-pyrazolo[3,4-g]quinoline

Rd, Titus; Ec, Kornfeld; Nd, Jones; Ja, Clemens; Eb, Smalstig; Rw, Fuller; Ra, Hahn; Hynes,; Nr, Mason; Dt, Wong; Mm, Foreman

doi:10.1021/jm00362a005

Cited by 117 publications

(12 citation statements)

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“…The present findings extend earlier reports that generalized dopamine receptor activation by apomorphine increases hor mone secretion by corticotrophs in vivo [6,15] and that dopa minergic agonists, particularly D-2 compounds, increase serum corticosterone levels in rats [8,9,28]. If D-2 receptors, indeed, exert stimulatory control over the secretion of CRF, then the ability of the general dopamine antagonist, haloperidol, to evoke corticotroph secretion [10,13,21,25] is most likely due to its blockade of D-1 receptors which are tonically inhibitory to CRF release.…”

Section: Discussionsupporting

confidence: 90%

A D-2 Dopaminergic Agonist Stimulates Secretion of Anterior Pituitary Immunoreactive β-Endorphin in Rats

Farah

Mueller²

1989

Neuroendocrinology

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Hypothalamic dopamine neurons are known to control circulating levels of immunoreactive β-endorphin (iβ-END) by inhibiting hormone secretion by the intermediate lobe (IL) of the pituitary gland. We examined the ability of the D-2 selective dopaminergic agonist, LY141865, to influence circulating levels of iβ-END in rats and found that in contrast to inhibiting IL secretion, LY141865 increased release of iβ-END from the anterior lobe (AL). Intraperitoneal injection of 1 mg/kg LY141865 transiently increased plasma levels of iβ-END by 7–30 min after drug treatment; plasma prolactin levels were maximally reduced within 15 min and throughout the remaining 2-hour time course of treatment. Doses of 0.3 and 1.0 mg/kg of LY141865 increased circulating iβ-END to 440 and 690%, respectively, of control levels (0.38 ± 0.12 ng/ml, mean ± SEM, n = 6). Lower doses of the D-2 agonist (0.01–0.1 mg/kg) failed to significantly affect plasma iβ-END. Sephadex G-50 chromatography of plasma pools revealed that virtually all of the increase due to LY141865 treatment was immunoreactivity resembling β-lipotropin in molecular size, the principal component of AL secretion of iβ-END. Furthermore, LY141865-evoked release was blocked by pretreatment of rats with dexamethasone (50 µg/kg i.p., 4 h) which inhibits AL but not IL secretion of pro-opiomelanocortin-derived peptides. Stimulation of iβ-END release by LY141865 was also inhibited by the general dopamine antagonist, haloperidol, (0.1–3.0 mg/kg i.p., 2 h) and by the D-2 selective antagonist, sulphide (100 µg/rat i.c.v., 4 h). These results indicate that the effects of LY141865 treatment on pituitary release of iβ-END are mediated by dopaminergic receptor activation, probably of the D-2 type, within the central nervous system. Since neither dopamine nor LY141865 directly influences AL secretion of iβ-END, the effects of D-2 receptor stimulation in vivo are probably mediated by actions of LY141865 on secretion of hypothalamic corticotropin-releasing factor, the principal physiologic stimulator of hormone secretion from pituitary corticotrophs.

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Section: Discussionsupporting

confidence: 90%

A D-2 Dopaminergic Agonist Stimulates Secretion of Anterior Pituitary Immunoreactive β-Endorphin in Rats

Farah

Mueller²

1989

Neuroendocrinology

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“…However, since this drug has affinity for all D2-like receptors, including D2R, D3R, and D4R (Titus et al ., 1983; Sokoloff et al, 1992; Gehlert et al 1992; Seeman and Van Tol, 1994), we used more selective pharmacological agents to assess the mechanisms underlying quinpirole-induced locomotion in adolescents and its enhancement by nicotine. L-741,626, an antagonist with a 10-fold preferential affinity for D2R over D3R (Bowery et al, 1996; Millan et al, 2000), dose-dependently antagonized quinpirole-induced locomotion in nicotine-pretreated animals and in saline-pretreated controls.…”

Section: Discussionmentioning

confidence: 99%

Nicotine modulation of adolescent dopamine receptor signaling and hypothalamic peptide response

et al. 2014

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Adolescence is a sensitive developmental period for limbic and dopamine systems that coincides with the typical age for onset of tobacco use. We have previously shown that a 4-day, low-dose nicotine (0.06 mg/kg) pretreatment enhances locomotor and penile response to the D2-like agonist, quinpirole (0.4 mg/kg), in adolescent but not adult rats. The present study is designed to determine mechanisms underlying this effect. Nicotine enhancement of adolescent quinpirole-induced locomotion was mediated by D2 receptors (D2Rs) since it was blocked by the D2R antagonist, L-741,626, but not by the D3R and D4R antagonists, NGB 2904 and L-745,870. Enhancement of quinpirole-induced erectile response was blocked by both L-741,626 and NGB 2904, indicating involvement of D3Rs. Whereas D2R binding was unaffected by adolescent nicotine pretreatment, effector coupling in the striatum was increased, as determined by GTPγS binding. Nicotine pretreatment enhanced quinpirole-induced c-fos mRNA expression in the hypothalamic paraventricular and supraoptic nuclei in adolescents only. Adolescent nicotine pretreatment enhanced c-fos mRNA expression in corticotropin releasing factor (CRF) cells of the paraventricular nucleus, and enhancement of penile erection was blocked by the CRF-1 receptor antagonist, CP 376,396. These findings suggest that adolescent dopamine and CRF systems are vulnerable to alteration by nicotine. This is the first evidence for a role of CRF in adolescent erectile response.

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“…It seems to be crucial to include compounds of many different chemical classes in work of this kind. Therefore, as agonist structures we included several aminotetralines Markstein, 1982, 1984), the D2 selective octahydrobenzo[g]quinoline Sandoz 205-50 1 { ( + ) -N , N diethyl-N'-[(3a,4aa, lop)-1,2,3,4,4a,5,10,10a-octahydro -7hydroxy -1propyl-3benzo[g]quinolinyl]sulfamide) (Closse et al, 1983, the abeorphine Sandoz 201-678 (Jaton et al, 1986, the D1-selective benzazepine SKF 38 39 3 (2,3,4,5-tetrahydro-7,8-dihydroxy-1 -phenyl-1 H-3-benzazepine) (Setler et al, 1978), and the D2-selective partial ergoline quinpirole (Titus et al, 1983), in addition to dopamine and apomorphine. The antagonists studied included butyrophenones, a benzamide, the D 1 -selective benzazepine SCH 23390 (Iorio et al, 1983), the phenothiazine, thioxanthene and dibenzo(di)azepine classes of tricyclic neuroleptics, and other structures.…”

Section: Discussionmentioning

confidence: 99%

Affinity Shifts Induced by Cations Do Not Reliably Predict the Agonistic or Antagonistic Nature of Ligands at Brain Dopamine Receptors

Urwyler¹

1987

Journal of Neurochemistry

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The effects of Ca2+ and Na+ ions on the affinities of rat striatal dopamine D1 and D2 receptors for a wide range of agonists and antagonists were investigated. These experiments were performed at 37 degrees C, since it was found that at this physiological temperature D2 receptor affinities for dopamine and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene were clearly lower than at room temperature. No correlation was found between the effects of the cations on the affinities of compounds for D1 and D2 receptors and their agonistic or antagonistic nature. On the other hand, the Hill coefficients of agonists but not of antagonists were consistently and significantly below unity, with either Ca2+ or Na+ ions present and at both receptors. This suggests the existence of yet another type of heterogeneity of D1 and D2 receptor forms, to which agonists but not antagonists are sensitive. It is thus concluded that changes in D1 and D2 receptor affinities induced by cations do not predict the agonistic or antagonistic nature of a compound. However, since dopamine itself was sensitive to Na+ or Ca2+ ions, this mechanism might play a role in the regulation of receptor affinities in synaptic transmission, in addition to that exerted by guanyl nucleotides.

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Resolution and absolute configuration of an ergoline-related dopamine agonist, trans-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H(or 2H)-pyrazolo[3,4-g]quinoline

Cited by 117 publications

References 4 publications

A D-2 Dopaminergic Agonist Stimulates Secretion of Anterior Pituitary Immunoreactive β-Endorphin in Rats

A D-2 Dopaminergic Agonist Stimulates Secretion of Anterior Pituitary Immunoreactive β-Endorphin in Rats

Nicotine modulation of adolescent dopamine receptor signaling and hypothalamic peptide response

Affinity Shifts Induced by Cations Do Not Reliably Predict the Agonistic or Antagonistic Nature of Ligands at Brain Dopamine Receptors

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