Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P08908 (5-HT1A)
5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The basal ganglia in the brain contains glutamate, dopamine, serotonin, noradrenaline, CCK, adenosine, opioid, cannabinoid, etc. These agents contribute to keep motor control and modulation of the agent may be a cue to the treatment of movement disorders. D1 or D2 dopamine receptor agonists increase locomotor activity in MPTP-treated common marmosets which showed decreased locomotor activity and decreased number of dopamine neurons in the substantia nigra. Using this model of parkinsonism, NMDA receptor antag-onists, antimuscarinic receptor antagonists, 5-HT1A receptor agonists, adenosine receptor antagonists were showed to reverse the impaired movement of the model animals. The results may contribute to the development of new drugs for the treatment of Parkinson's disease.
...
PMID:[The pharmacological and rational theory for the drug development of Parkinson's disease]. 1546 80

The role of the brain 5-HT1A receptor in cognition was examined in the water maze (WM) and passive avoidance (PA) tasks in the male rat. Pre-training administration of the 5-HT1A receptor agonist 8-OH-DPAT impaired WM performance and facilitated PA retention at low doses (0.01 and 0.03 mg/kg) and impaired PA retention at higher doses (0.1-1.0 mg/kg). The 5-HT1A receptor antagonist NAD-299 produced a dose-dependent facilitation of PA retention. In contrast, the 5-HT1A receptor antagonists NAD-299 and WAY-100635 failed to alter acquisition and retention in the WM. The impairments in WM and PA (but not facilitation in PA) induced by 8-OH-DPAT were blocked by NAD-299. Furthermore, NAD-299 prevented the PA impairments induced by the muscarinic antagonist scopolamine or the NMDA receptor antagonist MK-801. In contrast, NAD-299 and WAY-100635 failed to attenuate the WM impairment induced by scopolamine, probably due to the failure of 5-HT1A receptor blockade to attenuate the sensorimotor disturbances induced by scopolamine. These results indicate that 5-HT1A receptor stimulation and blockade result in opposite effects in two types of cognitive tasks in the rat, and that 5-HT1A receptor blockade can facilitate some aspects of cognitive function, probably via modulation of cholinergic and glutamatergic transmissions. This suggests that 5-HT1A receptor antagonists may have a potential role in the treatment of human degenerative disorders associated with cognitive deficits.
...
PMID:Analysis of the role of 5-HT1A receptors in spatial and aversive learning in the rat. 1582 55

Serotonin (5-HT) receptors are increasingly recognized as major targets for cognitive enhancement in schizophrenia. Several lines of evidence suggest a pathophysiological role for glutamate NMDA receptors in the prefrontal cortex in schizophrenia and associated disorders in attention and executive functioning. We investigated how the interactions between 5-HT1A and 5-HT2A and glutamate NMDA receptor mechanisms in the medial prefrontal cortex (mPFC) contribute to the control of different aspects of attentional performance. Rats were trained on a five-choice serial reaction time (5-CSRT) task, which provides indices of attentional functioning (percentage of correct responses), executive control (measured by anticipatory and perseverative responses), and speed. The competitive NMDA receptor antagonist CPP (50 ng/side) was infused directly into the mPFC 5 min after infusion of either 8-OH-DPAT (30 and 100 ng/side) or M100907 (100 and 300 ng/side) into the same brain area. Impairments in attentional functioning induced by CPP were completely abolished by both doses of 8-OH-DPAT or M100907. In addition, M100907 abolished the CPP-induced anticipatory responding but had no effects on perseverative over-responding, while 8-OH-DPAT reduced the perseverative over-responding but had no effects on anticipatory responding induced by CPP. The selective 5-HT(1A) receptor antagonist WAY100635 (30 ng/side) antagonized the effects of 8-OH-DPAT (100 ng/side). 8-OH-DPAT at 30 ng/side reduced the latency of correct responses in controls and CPP-injected rats and lowered the percentage of omissions in CPP-injected rats. The data show that 5-HT1A and 5-HT2A receptors in the mPFC exert opposing actions on attentional functioning and demonstrate a dissociable contribution of 5-HT1A and 5-HT2A receptors in the mPFC to different aspects of executive control such as impulsivity and compulsive perseveration.
...
PMID:Dissociable contribution of 5-HT1A and 5-HT2A receptors in the medial prefrontal cortex to different aspects of executive control such as impulsivity and compulsive perseveration in rats. 1619 87

In urethane-chloralose anesthetized, neuromuscularly blocked, ventilated rats, microinjection of NMDA (12 pmol) into the right fourth thoracic segment (T4) spinal intermediolateral nucleus (IML) immediately increased ipsilateral brown adipose tissue (BAT) sympathetic nerve activity (SNA; peak +492% of control), expired CO2 (+0.1%) heart rate (+48 beats min(-1)) and arterial pressure (+8 mmHg). The increase in BAT SNA evoked by T4 IML microinjection of NMDA was potentiated when it was administered immediately following a T4 IML microinjection of 5-hydroxytryptamine (5-HT, 100 pmol) or the 5-HT1A/5-HT7 receptor agonist, 8-OH-DPAT (600 pmol), (area under the curve: 184%, and 259% of the NMDA-only response, respectively). In contrast, T4 IML microinjection of the 5-HT2 receptor agonist, DOI (28 pmol) did not potentiate the NMDA-evoked increase in BAT SNA (101% of NMDA-only response). Microinjection into the T4 IML of the selective 5-HT1A antagonist, WAY-100635 (500 pmol), plus the 5-HT7 antagonist, SB-269970 (500 pmol), prevented the 5-HT-induced potentiation of the NMDA-evoked increase in BAT SNA. When administered separately, WAY-100635 (800 pmol) and SB-269970 (800 pmol) attenuated the 8-OH-DPAT-induced potentiation of the NMDA-evoked increase in BAT SNA through effects on the amplitude and duration of the response, respectively. The selective 5-HT2 receptor antagonist, ketanserin (100 pmol), did not attenuate the potentiations of the NMDA-evoked increase in BAT SNA induced by either 5-HT or 8-OH-DPAT. These results demonstrate that activation of 5-HT1A/5-HT7 receptors can act synergistically with NMDA receptor activation within the IML to markedly increase BAT SNA.
...
PMID:Brown adipose tissue sympathetic nerve activity is potentiated by activation of 5-hydroxytryptamine (5-HT)1A/5-HT7 receptors in the rat spinal cord. 1808 30

Catatonia and neuroleptic malignant syndrome (NMS) are uncommon disorders that can be life-threatening. Many researchers consider them as clinically divergent entities; however, they share similar and overlapping literature on causative agents, phenomenology, and treatment response. This hypothesis considers both disorders as a single entity that result from variable combinations of the following: 1) gamma-aminobutyric acid (GABA) hypoactivity at the GABAA receptor; 2) dopamine hypoactivity at the D2 receptor; 3) serotonin hyperactivity at the 5-HT1A receptor and hypoactivity at the 5-HT2A receptor; and 4) glutamate hypoactivity at the N-methyl-D-aspartate (NDMA) receptor. In this paper, evidence to support this hypothesis is limited to retrospective human studies of catatonia and NMS. The four components of the hypothesis are: 1) GABAA agonists have been shown to alleviate catatonia and NMS; 2) D2 antagonism is proportional to the relative likelihood of NMS and catatonia; 3) 5-HT1A agonism with 5-HT2A antagonism is implicated in catatonia and NMS; 4) NMDA receptor antagonists, such as phencyclidine and ketamine, reduce glutamate transmission. This hypothesis proposes that it is the interaction of these systems that prediposes, initiates, and maintains the twin syndromes of catatonia and NMS.
...
PMID:The universal field hypothesis of catatonia and neuroleptic malignant syndrome. 1819 53

It is known that the activation of 5-hydroxytryptamine receptor type 1A (5HT(1A) receptor) may protect against brain damage induced by transient global ischemia. The biochemical mechanisms that underlie this neuroprotective effect remain however to be fully elucidated. Given that serotonergic drugs may regulate N-methyl-d-aspartate (NMDA) receptor function, which is implicated in events leading to ischemia-induced neuronal cell death, and also stimulate the expression of brain-derived neurotrophic factor (BDNF), which is down-regulated in cerebral ischemia, we sought to determine the effects of the selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on the levels of NMDA receptor NR1 subunit and BDNF in gerbil hippocampus after transient global cerebral ischemia. Pretreatment with 8-OH-DPAT (1 mg/kg) prevented the neuronal loss in CA1 subfield 72 h after ischemia and also the dramatic decrease in BDNF immunoreactivity observed in this area at an earlier time. NMDA receptor NR1 levels in whole hippocampus were not affected 24 h after ischemia, but the levels of the subunit phosphorylated at the protein kinase A (PKA) site, pNR1(Ser897), were significantly increased, and this increase was prevented by the same 8-OH-DPAT dose, a probable consequence of the increased phosphatase 1 (PP1) enzyme activity found in ischemic gerbils pretreated with the 5-HT(1A) receptor agonist. The results indicate that both NR1 subunit phosphorylation and the neurotrophin BDNF account, at least in part, for the neuroprotective effect of 8-OH-DPAT on cell damage induced by global ischemia in the gerbil hippocampus and support the potential interest of 5-HT1A receptor activation in the search for neuroprotective strategies.
...
PMID:Neuroprotective effects of serotonin 5-HT 1A receptor activation against ischemic cell damage in gerbil hippocampus: Involvement of NMDA receptor NR1 subunit and BDNF. 1826 31

The mechanisms involved in the neuroprotective effect of serotonin 5-HT1A receptor agonists on brain damage induced by ischemia remain to be fully elucidated. Given that serotonergic drugs may regulate N-methyl-D-aspartate (NMDA) receptor function, which is implicated in events leading to ischemia-induced neuronal cell death, this study sought to determine the effects of the selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on the levels of NMDA receptor NR1 subunit in gerbil hippocampus after transient global cerebral ischemia. Pretreatment with 8-OH-DPAT (1 mg/kg) prevented the neuronal loss in CA1 subfield 72 h after ischemia. NMDA receptor NR1 levels in whole hippocampus were not affected 24 h after ischemia, but the levels of the subunit phosphorylated at the protein kinase A (PKA) site, pNR1(Ser897), were significantly increased, and this increase was prevented by the same 8-OH-DPAT dose, a probable consequence of the increased phosphatase 1 (PP1) enzyme activity found in ischemic gerbils pretreated with the 5-HT1A receptor agonist. The results suggest that NR1 subunit phosphorylation plays a role in the neuroprotective effect of 8-OH-DPAT on cell damage induced by global cerebral ischemia in the gerbil hippocampus and support the potential interest of 5-HT1A receptor activation in the search for neuroprotective strategies.
...
PMID:Serotonin 5-hT1A receptor activation prevents phosphorylation of NMDA receptor NR1 subunit in cerebral ischemia. 1830 76

New atypical antipsychotics show a greater affinity to serotonergic rather than to dopamine receptors, suggesting that serotonin (5-HT) has a major role in the pathophysiology and treatment of schizophrenia. The goal of this study was to characterise the response of pyramidal neurons in the medial prefrontal cortex (mPFC) to 5-HT and NMDA before and after administration of the NMDA receptor antagonist, MK-801 (dizocilpine), a well-validated pharmacological model of psychosis. mPFC pyramidal (glutamatergic) neurons were recorded in urethane-anaesthetised rats. The responses to NMDA and 5-HT were assessed using in vivo electrophysiology and microiontophoresis. The 5-HT2A/2C antagonist ritanserin and the 5-HT1A antagonist WAY100635 were used to block 5-HT responses. MK-801 decreased the NMDA-induced excitatory responses and increased NMDA-evoked burst activity among mPFC pyramidal neurons. Three subpopulations of pyramidal cells were identified according to their responses to 5-HT: excitation (33%), inhibition (40%) and non-response (27%). The inhibitory responses were blocked by WAY100635 in 100% of cases, but not by ritanserin; the excitatory responses were blocked by ritanserin in 75% of cases, but not by WAY100635. The administration of MK-801 potentiated the firing rate of excitatory responses but did not modify the inhibitory responses induced by microiontophoretic application of 5-HT. These results suggest that MK-801 modifies 5-HT synapses in the mPFC by potentiating the excitatory 5-HT2A/2C responses and attenuating NMDA excitations. These data indicate that 5-HT excitatory transmission is selectively impaired at the mPFC level in this pharmacological model of schizophrenia.
...
PMID:Potentiation of excitatory serotonergic responses by MK-801 in the medial prefrontal cortex. 1972 75

Serotonin 5-HT1A receptors are attractive targets for the development of improved antipsychotics. Indeed, extensive evidence in rodent models indicates that the activation of these receptors prevents extrapyramidal symptoms (EPS) induced by dopamine D2 receptor blockade, favors dopaminergic neurotransmission in the frontal cortex, has a positive influence on mood, and opposes NMDA receptor antagonist-induced cognitive and social interaction deficits. Therefore, 'third-generation' antipsychotics that combine partial agonism at 5-HT1A receptors with antagonism (or partial agonism) at D2 receptors have been investigated, including aripiprazole, perospirone, lurasidone (Dainippon Sumitomo Pharma Co Ltd), cariprazine (Gedeon Richter Ltd/Forest Laboratories Inc/Mitsubishi Tanabe Pharma Corp), PF-217830 (Pfizer Inc), F-97013-GD, F-15063 and bifeprunox. Such compounds appear to provide therapeutic benefits against a broader range of symptoms of schizophrenia, including negative symptoms and cognitive deficits that are poorly controlled by established antipsychotics. Recently developed compounds are essentially free of EPS liability, and exhibit little or no interaction at sites that are potentially involved in causing side effects such as weight gain, metabolic disorders or autonomic disturbance. These compounds differ in their balance of 5-HT1A/D2 receptor affinity and agonist or antagonist properties; such differences are likely to translate into distinct therapeutic profiles. The balance of 5-HT1A/D2 receptor properties should therefore be considered when selecting compounds as antipsychotic development candidates.
...
PMID:The importance of 5-HT1A receptor agonism in antipsychotic drug action: rationale and perspectives. 2057 76

We have studied the influence of the new adenine derivative VMA-99-82 on the exchange of monoamines and their metabolites in the brain of Wistar rats. In addition, the effect of VMA-99-82 on binding of 5-HT1A and 5-HT2A serotonin receptors and the system of 3H-serotonin reuptake in the brain synaptosomes has been studied in vitro. It is established that VMA-99-82 at a dose of 10 mg/kg has no affinity to 5-HT1A and 5-HT2A serotonin receptors and produces no effect on the reuptake of [3H]-5-HT. It is suggested that VMA-99-82 has a modulating effect on ion channel NMDA receptor complex of the glutamatergic system, which leads to the manifestation of antidepressant activity.
...
PMID:[Neurochemical mechanisms of antidepressant action of new adenine derivative]. 2139 10


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

---