Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, we found that the beta 1/beta 2 adrenoceptor blocking agent (-)penbutolol prevents behavioral and biochemical actions of the specific serotonin (5-HT)1A agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin. The putative 5-HT1 receptor antagonist profile of (-)penbutolol was further explored in the present study, using in vivo microdialysis methods to assess its effects on central 5-HT release. (+)Penbutolol and (-)pindolol were included for comparison purposes. In contrast to (-)pindolol (8.0 mg/kg s.c.), administration of (-)penbutolol (2.0 or 8.0 mg/kg s.c.) increased hippocampal 5-HT output. The (-)penbutolol-induced 5-HT response was dose-related, stereoselective and Ca(++)-dependent. In addition, the 5-HT response to (-)penbutolol was abolished by omitting the 5-HT reuptake blocker citalopram from the perfusion medium, suggesting the need for endogenous 5-HT tone. Local (-)penbutolol (1 microM) perfusion increased the 5-HT output per se, and also blocked 5-HT release suppression caused by the 5-HT1B receptor agonist CP-93,129. Furthermore, (-)penbutolol, but not its (+)antipode, prevented the decrease of 5-HT release induced by the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin. By comparison, the 5-HT1 receptor inactive beta adrenoceptor blockers metoprolol (beta 1) and ICI 118,551 (beta 2), given alone or in combination, did not increase 5-HT output and were ineffective in antagonizing the (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin response. The data indicate that (-)penbutolol possesses 5-HT1A and 5-HT1B autoreceptor antagonist properties, and may be a useful tool in studies of central 5-HT receptor-mediated function.
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PMID:In vivo microdialysis evidence for central serotonin1A and serotonin1B autoreceptor blocking properties of the beta adrenoceptor antagonist (-)penbutolol. 809 61

The relative importance of 5-HT1A and beta-adrenergic activities in the antiaggressive effects of (-)-penbutolol was studied in male mice. (-)-Penbutolol had high affinity for 5-HT1A receptors and beta-adrenoceptors, and antagonized the 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced 5-HT syndrome and the 8-hydroxy-2-(di-n-propylamin)tetralin (8-OH-DPAT)-induced discriminatory stimulus in rats. (-)-Penbutolol abolished aggressive behaviour (ED50 = 56 mumol/kg), and reversed the antiaggressive effects of 8-OH-DPAT and 1-(3-trifluoromethylphenyl)piperazine (TFMPP) (ED50 = 8.1 and 2.1 mumol/kg, respectively). (N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl-N-(2-pyridinyl) cyclohexanecarboxamide (WAY 100635) reversed the antiaggressive effects of 8-OH-DPAT (ED50 = 0.012 mumol/kg), but did not affect the antiaggressive effects of TFMPP. The antiaggressive effect of a submaximal dose of 8-OH-DPAT was markedly potentiated by beta-adrenoceptor antagonists without 5-HT1A receptor affinity, whereas (-)-penbutolol was effective at only one dose (4.5 mumol/kg). In conclusion, the 5-HT1A receptor antagonistic potency of (-)-penbutolol in aggressive mice is attenuated by beta-adrenoceptor-induced facilitation of serotonergic neurotransmission.
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PMID:The antiaggressive potency of (-)-penbutolol involves both 5-HT1A and 5-HT1B receptors and beta-adrenoceptors. 885 Nov 59

We have evaluated the effects of ligands with varying efficacies at beta-adrenoceptors and 5-HT1A receptors in three in vivo models reflecting pre- and/or postsynaptic 5-HT1A receptor activation. Forepaw treading in rats is mediated by postsynaptic 5-HT1A receptors, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamin)tetralin)-induced discriminative stimulus is predominantly mediated by postsynaptic, but presynaptic 5-HT1A receptors might also be involved, and footshock-induced ultrasonic vocalization involves predominantly presynaptic 5-HT1A receptors. In vitro receptor binding studies demonstrated high beta-adrenoceptor and 5-HT1A receptor affinity of (-)-penbutolol, high beta-adrenoceptor and 60 times lower 5-HT1A receptor affinity of (+)-penbutolol, high beta-adrenoceptor affinity and about 100 times lower 5-HT1A receptor affinity of pindolol and (-)-tertatolol, only affinity for beta-adrenoceptors of metoprolol and ICI 118,551 (erythro-D,L-1-(7-methylindan-4-yloxy)-3-isopropylamine-b utan-2-ol, and only affinity for 5-HT1A receptors of WAY 100.635 ((N-[2-[4- (2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexane-carboxamide). (-)-Penbutolol, (-)-tertatolol, pindolol and WAY 100.635 antagonized 5-MeODMT-induced (5-methoxy-N, N-dimethyltryptamine) forepaw treading in rats, and (+)-penbutolol, ICI 118,551 and metoprolol were inactive. (-)-Penbutolol, WAY 100.635 and (-)-tertatolol antagonized 8-OH-DPAT-induced discriminative stimulus in rats, pindolol and metoprolol showed a mixed antagonistic and agonistic profile. Pindolol antagonized footshock-induced ultrasonic vocalization in rats, tertatolol inhibited maximum 36% and WAY 100.635, (-)-penbutolol, (+)-penbutolol, metroprolol and ICI 118,551 were inactive. (-)-Penbutolol and WAY 100.635 reversed 8-OH-DPAT-induced inhibition of ultrasonic vocalization completely, (-)-tertatolol reversed maximum 52% and (+)-penbutolol and pindolol were inactive. It is concluded, that efficacies at 5-HT1A receptors can be estimated by applying a battery of in vivo test models that involve post- and presynaptic receptors to a variable degree. The in vivo ranking order of efficacy at 5-HT1A receptors was: WAY 100.635 = (-)-penbutolol < (-)-tertatolol < pindolol.
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PMID:Assessment of relative efficacies of 5-HT1A receptor ligands by means of in vivo animal models. 898 61