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

Contractile responses to serotonin (5-HT) of fundic smooth muscle strips isolated from both control and streptozotocin (STZ)-induced diabetic rats were investigated. Contrary to carbachol (CCh) which causes contractile hyperactivity in DM, 5-HT response tended to decrease in DM compared to that of the control. Pindolol (10(-5)M) increased the value of EC50 of the concentration-response to 5-HT about 2.5 times in both the control and DM. After treatment with pindolol, the maximal tension to 5-HT in DM significantly decreased compared to that of the control. Pindolol showed no effect on the contractile response to CCh. Pindolol significantly inhibited the relaxation caused by isoproterenol in DM more than in the control. Mianserin (10(-5) M) increased the EC50 of the response to 5-HT about 2-2.5 times in both groups, but did not cause a significant difference between the control and DM. The Ca(2+)-induced contraction caused hyperreactivity in DM in the presence of 10(-6) M CCh, but that in DM was not significantly different from the control in the presence of 10(-6) M 5-HT. Pretreatment of phorbol 12-myristate 13-acetate (PMA, 10(-5) M) significantly attenuated the response to 5-HT in the control, but not in DM. Results suggest that the contractile response to 5-HT in DM is related to the altered Ca2+ signal transduction system via disturbed protein kinase C (PKC) activity, and that there are alterations of receptor characteristics and of the density in 5-HT receptor subtypes, especially 5-HT1A, during DM development.
 ...
PMID:Alteration of contractile properties to serotonin in gastric fundus smooth muscle isolated from streptozotocin (STZ)-induced diabetic rats. 891 Feb 54

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.
 ...
PMID:Assessment of relative efficacies of 5-HT1A receptor ligands by means of in vivo animal models. 898 61

Pindolol has been shown to be a partial agonist at 5-HT1A receptors in preclinical studies. It has also been reported to inhibit the effects of other 5-HT1A partial agonists such as ipsapirone and buspirone on hormone secretion and body temperature in man, indicating its antagonist action at 5-HT1A receptors in man. To determine if pindolol has 5-HT1A agonist as well as antagonist effects in man, pindolol, 30 mg, p.o. and placebo, were given single blind in random order to 23 normal men with indwelling venous catheters and its effects on hormone secretion and body temperature noted. Pindolol significantly increased basal plasma cortisol concentrations, whereas it decreased plasma prolactin (PRL) concentrations and body temperature. The increase in plasma cortisol due to pindolol suggests a 5-HT1A agonist action and is consistent with a 5-HT1A partial agonist mechanism in man whereas the PRL effects are consistent with an antagonist action at 5-HT1A receptors. The effects of pindolol on plasma cortisol concentration and body temperature were significantly negatively correlated. Furthermore, these results indicate significant differences in the 5-HT1A-dependent regulation of PRL and the hypothalamo-pituitary-adrenal (HPA) axis and body temperature, and suggest that human basal PRL secretion is tonically stimulated by 5-HT1A mechanism whereas the HPA axis and body temperature are not. Since rodent studies suggest differences in 5-HT1A receptor sensitivity between males and females, the results reported here need to be replicated in females. These differences in the effect of pindolol are discussed in terms of receptor reserve theory.
 ...
PMID:Effect of pindolol on hormone secretion and body temperature: partial agonist effects. 902 79

Pindolol, a beta-adrenergic and presynaptic 5-HT1 vA antagonist, when added to specific serotonin reuptake inhibitors, potentiates the antidepressant action, leading to an earlier onset of effect. Following on from the suggestion that nefazodone, a specific serotonin reuptake inhibitor and antagonist of 5-HT2, improves 5-HT1A-mediated transmission, we used a pindolol and nefazodone combination treatment for major depressive disorder. Twenty outpatients underwent a 4-week trial. Patients were seen twice a week, and completed efficacy and safety measures including the 17-item Hamilton Depression Scale, the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impression scales. Results demonstrated significant improvement in all efficacy measures after one visit (2-4 days of treatment), with decreasing depression scores on all measures continuing throughout the trial. After 1 week of treatment, 15 out of 20 patients had experienced a 50% or greater reduction in their 17-item Hamilton Depression Scale scores. Remission rates were dramatic, with 40% of patients in remission after 1 week of treatment and 90% after 4 weeks. This open study of nefazodone-pindolol combination therapy suggests that this may be a new treatment option for patients with major depressive disorder; however, it needs to be replicated in a double-blind trial before conclusions regarding efficacy and safety can be made.
 ...
PMID:Fast onset: an open study of the treatment of major depressive disorder with nefazodone and pindolol combination therapy. 921 44

Administration of fluoxetine (10 mg/kg i.p.) caused a significantly greater increase in extracellular 5-HT levels in hypothalamus of rats adapted to a reverse light period (lights off 9:00 am-9:00 pm) than those adapted to the regular cycle (lights off 6:00 pm-6:00 am). Sequential administration of the antagonist 5-HT1A/beta-adrenergic receptors (-)-pindolol at 0.1, 0.3, 1, and 3 mg/kg s.c. significantly enhanced the fluoxetine-induced elevation of 5-HT levels in both groups of rats. (-)-Pindolol at 0.1 mg/kg potentiated the fluoxetine-induced elevation in 5-HT levels significantly higher in rats adapted to the reverse light cycle than in those accustomed to the regular light cycle. The greater effects of fluoxetine and the subsequent administration of (-)-pindolol in the reverse cycle group may relate to the difference in activity of 5-HT neurons in the dorsal raphe of conscious animals adapted to the two light periods.
 ...
PMID:Greater effects of fluoxetine and its combination with (-)-pindolol in elevating hypothalamic serotonin in rats during dark hours. 930 41

Pigeons were trained to discriminate 0.64 mg/kg (high dose) of 8-OH-DPAT (8-hydroxy-(2-di-n-propylamino)tetralin) from saline or were retrained to discriminate 0.16 mg/kg (low dose) of 8-OH-DPAT from saline. This resulted in a decrease of the ED50 for recognition of the 8-OH-DPAT cue from 0.14 to 0.04 mg/kg. Partial agonists for the 5-HT1A receptor (e.g., buspirone) were generalized fully in the low dose condition, but only partially in the high dose condition. Full antagonists, such as N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide (WAY-100635), antagonized the 8-OH-DPAT cue in both groups without producing generalization in either group. (-)-Pindolol produced full generalization in the low dose group, but antagonized the high dose stimulus cue. The behavioral effects of other compounds with 5-HT1A receptor activities (4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-pyridinyl-benz ami de hydrochloride (p-MPPI): (-)-1-(1H-indol-4-yloxy)-3-(cyclohexylamino)-2-propanol maleate ((-)-LY206130); racemic pindolol and idazoxan) also differed between groups. Comparing results obtained using differing training doses in the drug discrimination paradigm simplifies determination of the full agonist, partial agonist, or antagonist properties of compounds.
 ...
PMID:Differentiation of 5-HT1A receptor ligands by drug discrimination. 931 23

Experiments were carried out using rats to investigate whether 5-HT1A neural mechanisms are involved in lithium-induced conditioned taste aversion (CTA). We found that the 5-HT1A antagonists p-MPPI and pindolol caused CTA similar to that produced by LiCl. The 5-HT1A agonist 8-OH-DPAT counteracted lithium-induced CTA. Pindolol dose-dependently abolished effects of 8-OH-DPAT on LiCl-induced CTA. These findings support the notion that lithium has antagonistic actions on 5-HT1A receptors. Inhibition of 5-HT synthesis by PCPA failed, however, to prevent lithium-induced CTA. Evidently, mechanisms other than those governed solely by 5-HT are also involved in lithium-induced CTA.
 ...
PMID:5-HT1A receptors in lithium-induced conditioned taste aversion. 933 80

The effect of acute administrations of three doses of imipramine (1, 5 and 10 mg/kg s.c.), a widely used tricyclic antidepressant, on extracellular levels of serotonin (5-HT) has been studied by intracerebral microdialysis in raphe nuclei and prefrontal cortex of conscious rats. Imipramine 1 mg/kg s.c. did not change extracellular 5-HT in either raphe nuclei and prefrontal cortex. However, with the dose of 5 mg/kg s.c. imipramine induced in raphe nuclei, a brief increase of extracellular 5-HT followed by a lowering (55-65% basal release) of the neurotransmitter. The same dose of imipramine decreased (60-70% of basal value) extracellular 5-HT in prefrontal cortex. Imipramine 10 mg/kg s.c. significantly increased 5-HT levels in both raphe nuclei (190 +/- 20% above basal value) and prefrontal cortex (280 +/- 15% above basal value). Pretreatment with (-)pindolol (5 mg/kg s.c.), a non-selective 5-HT1A subtype receptor antagonist, 30 min before imipramine 5 mg/kg, modified the effect of the antidepressant: an increase, instead of a decrease, on prefrontal cortex dialysate 5-HT was observed. (-)Pindolol (10 mg/kg s.c.) increased extracellular 5-HT in both raphe nuclei (155 +/- 20% above basal value) and prefrontal cortex (160 +/- 8% above basal value). These data show that acute administration of imipramine modifies extracellular 5-HT at the level of the raphe nuclei and prefrontal cortex. 5-HT1A autoreceptors in the raphe nuclei, which this study suggests to be tonically active, may be stimulated after systemic administration of high doses of imipramine.
 ...
PMID:Effects of imipramine on raphe nuclei and prefrontal cortex extracellular serotonin levels in the rat. 945 83

It has been proposed that the arylalkylamine, (-)pindolol, potentiates the therapeutic action of antidepressant drugs in humans by blockade of 5-HT1A autoreceptors. Its interactions at human 5-HT1A receptors have not, however, been directly characterized. Herein, we demonstrate that (-)pindolol exhibits nanomolar affinity at human 5-HT1A receptors expressed in Chinese Hamster Ovary cells (CHO-h5-HT1A; Ki = 6.4 nmol/L). In a functional test of receptor-mediated G-protein activation (stimulation of [35S]-GTP gamma S binding) (-)pindolol displays an efficacy of 20.3% relative to the endogenous agonist, 5-HT (= 100%). (-)Pindolol also antagonizes 5-HT (100 nmol/L)-stimulated [35S]-GTP gamma S binding, reducing it to 19.8% of control binding. These data indicate that (-)pindolol acts as a (weak) partial agonist at CHO-h5-HT1A receptors and that it blocks the action of 5-HT at these sites.
 ...
PMID:Agonist and antagonist actions of (-)pindolol at recombinant, human serotonin1A (5-HT1A) receptors. 953 53

The present study was undertaken to identify the receptor subtypes involved in (+/-) pindolol's ability to enhance the effects of antidepressant drugs in the mouse forced swimming test. Interaction studies were performed with S 15535 (presynaptic 5-HT1A receptor agonist) and methiothepin (5-HT1B autoreceptor antagonist) in an attempt to attenuate or potentiate antidepressant-like activity. (+/-) Pindolol was tested in combination with selective agonists and antagonists at 5-HT1, 5-HT2 and 5-HT3 receptor subtypes. Pretreatment with S 15535 and methiothepin attenuated the activity of paroxetine, fluvoxamine and citalopram (32 mg/kg, i.p.; P < 0.01). (+/-) Pindolol (32 mg/kg, i.p.) induced significant anti-immobility effects when tested in combination with 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU 24969) (1 mg/kg, i.p.; P < 0.05), 1-(2-methoxyphenyl)-4-[-(2-phthalimido) butyl]piperazine) (NAN 190) (0.5 mg/kg; P < 0.05) and ondansetron (0.00001 mg/kg, i.p.; P < 0.01). Pretreatment with NAN 190 (0.5 mg/kg, i.p.) potentiated the effects of RU 24969 (1 mg/kg, i.p.; P < 0.05) and (+/-) pindolol (32 mg/kg, i.p.; P < 0.05) in the forced swimming test, as did ondansetron (0.00001 mg/kg, i.p.). Significant additive effects were induced when RU 24969 (1 mg/kg, i.p.) was tested in combination with NAN 190 (0.5 mg/kg, i.p.; P < 0.05), (+/-) pindolol (32 mg/kg, i.p.; P < 0.05) and ondansetron (0.0000 mg/kg, i.p.; P < 0.05). 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1 mg/kg, i.p.) or ketanserin (8 mg/kg, i.p.) did not induce significant antidepressant-like effects with any of the agonists/antagonists tested. The results of the present study suggest that pindolol is acting at presynaptic 5-HT1B serotonergic receptors, in addition to the 5-HT1A subtype, in augmenting the activity of antidepressants in the mouse forced swimming test.
 ...
PMID:Pindolol does not act only on 5-HT1A receptors in augmenting antidepressant activity in the mouse forced swimming test. 956 7


<< Previous 1 2 3 4 5 6 Next >>