Non-serotonergic potentiation by (-)-pindolol of DOI-induced forward locomotion in rats: possible involvement of beta-adrenoceptors?.
[1] We have previously shown that the beta-adrenergic/5-HT1 receptor partial agonist (-)-pindolol (2.0-32.0 micromol kg(-1)) enhances the increase in forward locomotion in rats produced by the 5-HT2 receptor agonist DOI (0.7 micromol kg(-1)) via net activation of post-synaptic 5-HT2 receptors. [2] It was found that neither the 5-HT1A receptor agonist and partial agonist, (+/-) 8-OH-DPAT (0.2-2.4 micromol kg(-1)) and (S)-(-)-UH-301, respectively, nor the 5-HT1A receptor antagonist WAY-100635 (0.09-1.5 micromol kg(-1)), substituted for (-)-pindolol in this in vivo behavioral model. [3] This also applies to the 5-HT1B receptor agonist and antagonist anpirtoline (0.3-4.0 micromol kg(-1)) and isamoltane (1.0-64.0 micromol kg(-1)), respectively. Neither of these compounds mimicked (-)-pindolol in its interactions with DOI. [4] The (-)-pindolol/DOI-induced increase in forward locomotion could be antagonized by the beta1 adrenoceptor antagonist betaxolol (24 micromol kg(-1)). [5] It is suggested that the intrinsic efficacy of (-)-pindolol at beta-adrenoceptors is an important aspect of its in vivo pharmacodynamic profile.
Kaur
P
P
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Ahlenius
S
S
D006916:5-Hydroxytryptophan / Q000378:metabolism; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D015784:Betaxolol / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000096:biosynthesis; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004357:Drug Synergism; D007215:Indophenol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010869:Pindolol / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012110:Reserpine / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D018759:Adrenergic Uptake Inhibitors; D000319:Adrenergic beta-Antagonists; D015306:Biogenic Monoamines; D010879:Piperazines; D010880:Piperidines; D011412:Propanolamines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C113896:dimethoxy-4-indophenyl-2-aminopropane; C064282:UH 301; C075631:anpirtoline; D007215:Indophenol; D004295:Dihydroxyphenylalanine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012110:Reserpine; C058392:isamoltane; D010869:Pindolol; D006916:5-Hydroxytryptophan; D015784:Betaxolol