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)

Amperozide is an atypical antipsychotic drug with high affinity for the serotonin 5-HT2 receptor but with low affinity for the dopamine D1 and D2 receptors. Amperozide dose-dependently increased the level of plasma corticocorticosterone in the rat. The effect of amperozide on plasma corticosterone was not inhibited by pretreatment with the 5-HT1A receptor antagonist pindolol or the 5-HT2 receptor antagonist ritanserin. Nor was it inhibited by the dopamine D2 receptor antagonist haloperidol. In contrast to ritanserin, amperozide did not antagonize plasma corticosterone elevation elicited by the serotonin receptor agonist MK-212. Similar to the serotonin uptake inhibitor fluoxetine, amperozide (0.5 mg/kg) significantly (p < 0.05) blocked p-chloroamphetamine (PCA) induced corticosterone release 4 and 16 hrs after amperozide administration. However, amperozide significantly increased the plasma corticosterone concentration also in rats pretreated with parachlorophenylalanine (PCPA). These data suggest that other mechanisms than a 5-HT uptake inhibitory effect are involved in the acute stimulation of corticosterone by amperozide.
 ...
PMID:The effect of amperozide, a new antipsychotic drug, on plasma corticosterone concentration in the rat. 135 66

The potencies of 5-methoxy-N, N-dimethyltryptamine (central 5-hydroxytryptamine 1 receptor agonist) and 8-hydroxy-2-(di-n-propylamino) tetralin (central 5-hydroxytryptamine 1A receptor agonist) in eliciting head-weaving behaviour were studied in streptozotocin-diabetic mice and a group of control animals. Both drugs induced head-weaving behaviour in the streptozotocin-diabetic mice and control animals, but the potencies of these 5-hydroxytryptamine 1 agonists were reduced in the streptozotocin-diabetic mice. The numbers of head weaves elicited in the streptozotocin-diabetic and control animals by the two drugs were suppressed by pre-treatment with propranolol (5-hydroxytryptamine 1A receptor antagonist) and methysergide (5-hydroxytryptamine 1 and 2 receptor antagonist), but not by ketanserin (5-hydroxytryptamine 2 receptor antagonist), confirming the involvement of the 5-HT1A receptor. Pretreatment with nicotinamide before administering streptozotocin prevented streptozotocin-induced hyperglycaemia and restored the inhibition of head-weaving behaviour observed in streptozotocin-diabetic mice. Insulin injection, which partially prevented streptozotocin-induced hyperglycaemia, completely prevented reduction of the number of head weaves elicited by 5-methoxy-N, N-dimethyltryptamine in streptozotocin-diabetic mice. These results suggest that the reduced response to 5-HT1 agonists in streptozotocin-diabetic mice may be caused by the depletion of insulin.
 ...
PMID:Effects of two 5-hydroxytryptamine agonists on head-weaving behaviour in streptozotocin-diabetic mice. 183 8

A dosage regimen of lysergic acid diethylamide (LSD) that reliably produces behavioral tolerance in rats was evaluated for effects on neurotransmitter receptor binding in rat brain using a variety of radioligands selective for amine receptor subtypes. Daily administration of LSD [130 micrograms/kg (0.27 mumol/kg) intraperitoneally (IP)] for 5 days produced a decrease in serotonin2 (5-hydroxytryptamine2, 5-HT2) binding in cortex (measured 24 hours after the last drug administration) but did not affect binding to other receptor systems (5-HT1A, 5-HT1B, beta-adrenergic, alpha 1- or alpha 2-adrenergic, D2-dopaminergic) or to a recognition site for 5-HT uptake. The decrease was evident within 3 days of LSD administration but was not demonstrable after the first LSD dose. Following 5 days of LSD administration the decrease was still present 48 hours, but not 96 hours, after the last administration. The indole hallucinogen psilocybin [1.0 mg/kg (3.5 mumol/kg) for 8 days] also produced a significant decrease in 5HT2 binding, but neither the nonhallucinogenic analog bromo-LSD [1.3 mg/kg (2.4 mumol/kg) for 5 days] nor mescaline [10 mg/kg (40.3 mumol/kg) for 5 or 10 days] affected 5-HT2 binding. These observations suggest that LSD and other indole hallucinogens may act as 5-HT2 agonists at postsynaptic 5-HT2 receptors. Decreased 5-HT2 binding strikingly parallels the development and loss of behavioral tolerance seen with repeated LSD administration, but the decreased binding per se cannot explain the gamut of behavioral tolerance and cross-tolerance phenomena among the indole and phenylethylamine hallucinogens.
 ...
PMID:Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain. 196 70

Microinjections of serotonin (5-HT) delivered into the nucleus tractus solitarius (NTS) elicit opposite cardiovascular effects depending on the doses used; blood pressure and heart rate are decreased by low doses but increased by high doses. To examine this apparent contradiction, we compared cardiovascular and sympathetic nerve responses elicited in anesthetized rats by using glass micropipettes to inject 5-HT, the vehicle alone or various 5-HT agonists or antagonists into the NTS. Low (0.2 nmol) 5-HT doses lowered mean arterial pressure, heart rate and renal nerve activity consistently. By contrast, high (2 nmol) doses were relatively ineffective as were similar injections of the vehicle alone or of 5-HT1A or 5-HT2A agonists. Systemic cholinergic blockade with methylatropine abolished the bradycardia produced by low 5-HT doses with little or no effect on attendant depressor and sympathoinhibitory responses. Local blockade induced by injecting the 5-HT1A antagonist, WB4101, into the NTS abolished all 5-HT responses, but that induced with the 5-HT2 antagonist, ketanserin, inhibited the same responses only partially. These results suggest that low 5-HT doses injected into the NTS act mainly on 5-HT1A receptors to cause bradycardia through parasympathetic stimulation and lower blood pressure through sympathetic inhibition.
 ...
PMID:Cardiovascular and sympathetic effects of injecting serotonin into the nucleus tractus solitarius in rats. 200 78

Affinities of drugs for 21 indolealkylamine derivatives, some with putative hallucinogenic activity, were determined at 5-HT1A, 5-HT2A and 5-HT2B recognition sites, using radioligand competition studies. Nearly all of the derivatives displayed greatest potency for the 5-HT2A receptor, labelled by [125I]R-(-)DOI in the cortex of the rat. Most derivatives displayed 2-10 times lower affinity at the HT2B receptor labelled by [3H]ketanserin in bovine cortex. Derivatives lacking ring substituents displayed lower affinities for all of the recognition sites, compared to derivatives substituted in the 4- or 5-position of the indole ring. The 4-hydroxylated derivatives displayed 25-380-fold selectivity for the 5-HT2A site, vs the 5-HT1A site, while the 5-substituted derivatives displayed approximately equal potency at the 5-HT1A and 5-HT2A sites. Affinity of all the compounds at the 5-HT2B site was greater than 300 nM. The 6-substituted derivatives displayed greater than micromolar affinities for all of the 5-HT recognition sites examined. The size of the N,N-dialkyl substituent was a secondary determinant of affinity, with groups larger than N,N-diisopropyl resulting in a marked reduction in affinity at both the 5-HT2A and 5-HT1A recognition sites. This study demonstrated that hallucinogenic 4-hydroxy-indolealkylamines, like psychotomimetic phenylisopropylamines, bind potently and selectively to the 5-HT2A recognition site, labelled by [125I]R-(-)DOI. This provides further evidence indicating that this recently described subtype of the 5-HT2 receptor may partially mediate the action of hallucinogenic agents.
 ...
PMID:Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes. 213 86

The anatomical distribution of [3H]norharman binding sites was determined by quantitative autoradiography in rat brain slices. They are enriched in hypothalamic, thalamic, accumbens and amygdaloid nuclei as well as in hippocampal, neocortical and olfactory-related structures. The distribution pattern differs from that of other previously described receptors or binding sites (e.g. monoamine oxidase, benzodiazepine, tryptamine, 5-hydroxytryptamine receptors (5-HT1A, 5-HT1B, 5-HT1C, 5HT2], which suggests that a unique class of [3H]norharman binding sites exists in the rat brain. The findings are consistent with previous experiments which showed high affinity binding sites for [3H]norharman in rat brain membranes (KD 1.552 nM; autoradiography KD 5.5 nM). A correspondence in the displacing activity of drugs was found for both methods (crude membrane fraction: harman much greater than tryptamine much greater than 5-hydroxytryptamine greater than N-methyl-beta-carboline-3-carboxamide (FG 7142) = diazepam; autoradiography: harman much greater than tryptamine much greater than FG 7142 greater than 5-hydroxytryptamine greater than diazepam). Provided that the binding sites represent functional receptors, the present anatomical findings may explain the biological effects of norharman, e. g. pro-conflict behaviour (limbic-hypothalamic structures), tonic-clonic convulsions (limbic-cortical structures) and alterations of locomotor activity (accumbens nucleus).
 ...
PMID:Quantitative autoradiography of [3H]norharman [( 3H]beta-carboline) binding sites in the rat brain. 215 25

There is increasing evidence that neuroendocrine and temperature responses in humans can be employed to study the functional sensitivity of different 5-HT receptor subtypes. The evidence suggests that the PRL response to LTP is mediated by 5-HT1 receptors, perhaps the 5-HT1A subtype, though further studies are needed to confirm this effect. It is uncertain whether the PRL responses to other 'presynaptic' challenges of 5-HT function, for example, fenfluramine, are mediated by the same post-synaptic 5-HT receptor subtype as that for LTP. Conversely it seems likely that agonists which stimulate 5-HT2/1C receptors increase both plasma PRL and ACTH in humans. There is also evidence that 5-HT1A receptors can increase ACTH secretion. This suggests that in humans as in animals both the 5-HT1A and 5HT2/1C receptors can facilitate ACTH release, though the significance of this dual control is not understood. It is also possible that both 5-HT1A and 5-HT2/1C receptors stimulate PRL release, but 5-HT1A receptors may have a more prominent role in GH secretion. In both human and animal studies 5-HT1A and 5-HT2 receptor agonists may produce opposite effects on body temperature. These recent developments in 5-HT neuroendocrinology have been of great interest, but much is still uncertain. Progress in this field will be considerably advanced by the availability of new selective 5-HT receptor ligands, particularly selective receptor antagonists.
 ...
PMID:Endocrinological responses to 5-HT. 225 13

The effects of ethanol on serotonin (5-hydroxytryptamine, 5-HT) receptor binding in rat and mouse brain were determined under in vitro conditions and in mouse brain following seven days of ethanol ingestion. 5-HT1A receptor characteristics were measured utilizing the agonist [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([ 3H]DPAT), and 5HT2 receptor-binding studies utilized the antagonist [3H]ketanserin. At the highest concentration of ethanol tested in vitro (680 mM), there was only 25% inhibition of [3H]DPAT binding in rat and mouse brain and 14% inhibition of [3H]ketanserin binding in rat brain. Effects of an anesthetic concentration of ethanol (100 mM) on agonist binding in the presence and absence of the guanine nucleotide GTP were also evaluated in vitro in mouse brain. In no case did ethanol (100 mM) significantly affect 5-HT1A or 5-HT2 receptor-binding characteristics. When 5-HT receptor characteristics were measured after mice consumed ethanol for seven days, there was no change in either 5-HT1A or 5-HT2 receptor-binding properties in any of the brain areas examined.
 ...
PMID:Ethanol does not affect serotonin receptor binding in rodent brain. 252 20

The radioligand binding characteristics of 125I-R-(-)4-iodo-2,5-dimethoxyphenylisopropylamine [125I-R-(-)DOI] and 3H-ketanserin were compared in rat and bovine cortical membranes. In rat cortex, 125I-R-(-)DOI labels a relatively low density of binding sites (Bmax = 2.5 +/- 0.2 pmol/gm tissue) with high affinity (KD = 0.63 +/- 0.09 nM). In bovine cortex, specific binding of 125I-R-(-)DOI represents less than 20% of total binding at radioligand concentrations above 0.6 nM, and, therefore, the data cannot be analyzed adequately by Scatchard transformation. By contrast, 3H-ketanserin displays saturable, specific high-affinity binding in both rat cortex (KD = 1.0 +/- 0.1 nM; Bmax = 11 +/- 0.4 pmol/gm tissue) and bovine cortex (KD = 1.2 +/- 0.2 nM; Bmax = 5.3 +/- 0.4 pmol/gm tissue). Ki values for 30 drugs were determined for 125I-R-(-)DOI-labeled sites in rat cortex and 3H-ketanserin-labeled sites in bovine cortex. 5-Hydroxytryptamine (5-HT) displays 250-fold higher selectivity for the 125I-R-(-)DOI-labeled sites (Ki = 3.0 +/- 0.7 nM) than for the 3H-ketanserin-labeled sites (Ki = 750 +/- 50 nM). Structural congeners of R-(-)DOI display 80- to 160-fold higher affinity for the 125I-R-(-)DOI binding site than for the 3H-ketanserin-labeled binding site. d-LSD and putative 5-HT2 antagonists are approximately equipotent at both sites. Significant correlations were found between drug affinities for 125I-R-(-)DOI-labeled sites in rat cortex and putative 5-HT2A sites labeled previously by 77Br-R-(-)DOB (r = 0.93, p less than 0.01), putative 5-HT2B sites labeled by 3H-ketanserin in bovine cortex (r = 0.63, p less than 0.01), and 5-HT1C binding sites that have been characterized by other investigators (r = 0.78, p less than 0.01). No significant correlations were found between drug affinities for 125I-R-(-)DOI-labeled sites in rat cortex and 5-HT1A, 5-HT1B, 5-HT1D, or 5-HT3 sites, as determined by previous investigators. We conclude that 125I-R-(-)DOI labels a novel 5-HT binding site subtype (tentatively designated the 5-HT2A binding site) that is present in rat cortex but is either absent or minimally present in bovine cortex. By contrast, 3H-ketanserin labels both the putative 5-HT2A site in rat cortex as well as a separate, distinct recognition site that is present in both rat and bovine cortex, tentatively designated the 5-HT2B site.
 ...
PMID:Differentiation of 5-hydroxytryptamine2 receptor subtypes using 125I-R-(-)2,5-dimethoxy-4-iodo-phenylisopropylamine and 3H-ketanserin. 279 35

1. The pharmacological profile of niaprazine was investigated using in vitro ligand binding techniques. 2. Niaprazine exhibits a low affinity for the vesicular monoamine transporter and for D2, alpha 2, beta, H1 and muscarinic cholinergic receptors. Niaprazine, particularly the (+)stereoisomer, has a higher affinity for alpha 1 (Ki = 77 nM) and 5-HT2 (Ki = 25 nM) binding sites, but is poorly recognized by 5-HT1A and 5-HT1B binding sites (Ki sigma mciroM). In contrast, p-fluoro-phenylpiperazine, a major metabolite of niaprazine, exhibits a higher affinity for the 5-HT1 subclasses than for the 5HT2 class. 3. These results suggest that the pharmacological properties of niaprazine reflect both its non-reserpinic catecholamine depletor effect and its action on alpha 1 and 5-HT2 receptors. A role of p-fluoro-phenylpiperazine via 5-HT1 sites cannot be excluded.
 ...
PMID:Molecular pharmacology of niaprazine. 285 85


1 2 3 4 5 6 7 8 9 10 Next >>