Abstract：
:(5R,6R)6-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3 .2.1]octane (PTAC) is a potent muscarinic receptor ligand with high affinity for central muscarinic receptors and no or substantially less affinity for a large number of other receptors or binding sites including dopamine receptors. The ligand exhibits partial agonist effects at muscarinic M2 and M4 receptors and antagonist effects at muscarinic M1, M3 and M5 receptors. PTAC inhibited conditioned avoidance responding, dopamine receptor agonist-induced behavior and D-amphetamine-induced FOS protein M5 expression in the nucleus accumbens without inducing catalepsy, tremor or salivation at pharmacologically relevant doses. The effect of PTAC on conditioned avoidance responding and dopamine receptor agonist-induced behavior was antagonized by the acetylcholine receptor antagonist scopolamine. The compound selectively inhibited dopamine cell firing (acute administration) as well as the number of spontaneously active dopamine cells (chronic administration) in the limbic ventral tegmental area (A10) relative to the non-limbic substantia nigra, pars compacta (A9). The results demonstrate that PTAC exhibits functional dopamine receptor antagonism despite its lack of affinity for the dopamine receptors and indicate that muscarinic receptor partial agonists may be an important new approach in the medical treatment of schizophrenia.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Bymaster FP,Shannon HE,Rasmussen K,Delapp NW,Mitch CH,Ward JS,Calligaro DO,Ludvigsen TS,Sheardown MJ,Olesen PH,Swedberg MD,Sauerberg P,Fink-Jensen Adoi
10.1016/s0014-2999(98)00487-7subject
Has Abstractpub_date
1998-09-04 00:00:00pages
109-19issue
2-3eissn
0014-2999issn
1879-0712pii
S0014-2999(98)00487-7journal_volume
356pub_type
杂志文章abstract：:Binding of the radioligand [125I]iodoclonazepam to three different areas of rat brain (cerebellum, hippocampus and striatum) has been characterised. In all three regions binding is rapid, saturable and of high affinity (cerebellum Bmax = 1.49 +/- 0.3 pmol/mg of protein, Kd = 0.39 +/- 0.06 nM; hippocampus Bmax = 1.5 +/...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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abstract：:Extracellular diadenosine polyphosphates (ApnA) are recently considered as an endogenous signaling compounds with transmitter-like activity which present in numerous tissues, including heart. It has been demonstrated previously that extracellular ApnA cause alteration of the heart functioning via purine receptors in d...
journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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abstract：:The binding profile of cyclazosin, a new prazosin-related alpha 1-adrenoceptor antagonist, at alpha 1-, alpha 2-adrenoceptors, dopamine D2 and 5-HT1A receptors was compared to that of 5-methylurapidil, spiperone, risperidone and other prazosin-related ligands. In addition, cyclazosin was investigated at native and clo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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abstract：:Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine. By means of alkaline phosphatase activity and osteocalcin enzyme-linked immunosorbent assay (ELISA), we have shown that piceatannol exhibits a significant induction of differentiation in immortalized fetal osteoblasts (hFOB...
journal_title：European journal of pharmacology
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更新日期：2006-12-03 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90261-8
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90094-4
更新日期：1986-06-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.172980
更新日期：2020-04-15 00:00:00
abstract：:The influence of inflammatory cells on airway reactivity was investigated on arachidonic acid-induced relaxations of guinea-pig trachea and on arachidonic acid metabolism in guinea-pig tracheal epithelial cells. The presence of either eosinophils or neutrophils (1.0 x 10(7) cells/ml), from bronchoalveolar lavage, decr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(96)00736-4
更新日期：1996-12-19 00:00:00
