SEARCH · PubMed Health

Results for “Receptor, Serotonin, 5-HT1A”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1992

Mediation of serotonin hyperalgesia by the cAMP second messenger system.

In this study we have evaluated the second messenger system that might couple 5-HT1A receptor activation to produce peripheral hyperalgesia. The intradermal injection of the serotonin (5-hydroxytryptamine; 5-HT) receptor agonist for the 1A receptor subset (5-HT1A), (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthaline hydrobromide (8-OH DPAT) produces a dose-dependent hyperalgesia which was attenuated by a cAMP kinase inhibitor (the R-isomer of cyclic adenosine-3'-5'-monophosphate), but prolonged by the inhibition of endogenous phosphodiesterase by rolipram, supporting a role for the cAMP second messenger system. The 5-HT1A receptor agonist, 8-OH-DPAT, and the adenyl cyclase activator, forskolin administered together, produced an additive hyperalgesia, suggesting that the 5-HT1A receptor in peripheral terminals of the primary afferent neurons is positively coupled to the cAMP second messenger system in producing hyperalgesia. The inability of pertussis toxin to inhibit 8-OH DPAT-induced hyperalgesia further supports this hypothesis. The coupling of the 5-HT1A receptor to the cAMP second messenger system appears to be through guanine regulatory proteins since guanosine 5'-O-(3-thiotriphosphate) and cholera toxin both markedly enhanced 8-OH DPAT hyperalgesia. In further support of the role of guanine nucleotide regulatory proteins, guanosine 5'-O-(2-thiodiphosphate), as well as activators of inhibitory guanine regulatory proteins (the mu-opioid agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, and the adenosine A1 agonist, N6-cyclopentyladenosine, significantly attenuated 8-OH DPAT hyperalgesia.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1992

The influence of serotoninergic drugs on dopaminergic neurotransmission in rat substantia nigra, striatum and limbic forebrain in vivo.

The effects of serotoninergic drugs on dopaminergic neurotransmission in the substantia nigra, the striatum and the limbic forebrain of rat have been investigated. The accumulation of 3-methoxytyramine (3-MT) following inhibition of monoamine oxidase with pargyline was used as an indirect measure of dopamine (DA) activity in vivo. The effects of the following serotoninergic drugs were tested: the 5-HT1A receptor agonist 8-OH-DPAT, the 5-HT1B receptor agonist trifluoromethyl-phenylpiperazine (TFMPP), CGS 12066 B and RU 24969, the 5-HT1A/1B antagonist (+/-)pindolol, the 5-HT2/1C receptor antagonist ritanserin, the 5-HT2/1C receptor agonist DL-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), the 5-HT3 receptor antagonist BRL 43694, the unselective 5-HT receptor antagonist methiothepin, and carbidopa + L-5-hydroxytryptophan (L-5-HTP) to achieve a general, unselective stimulation of multiple 5-HT receptors. In the substantia nigra, carbidopa + 5-HTP treatment increased the 3-MT accumulation by 26% and decreased the DA concentration to 67% of controls, tentatively suggesting a 5-HTP-induced displacement of nigral DA. A minor, non dose-related reduction in nigral 3-MT was seen after the 5-HT1A receptor agonist 8-OH-DPAT. None of the other serotonin receptor acting drugs induced any pronounced effect on the nigral 3-MT accumulation. Taken together, the findings provide little support for the idea that one single 5-HT receptor subtype serves a modulatory function on DA activity in the substantia nigra. In the striatum and the limbic forebrain, trifluoromethyl-phenylpiperazine dose-dependently increased the 3-MT accumulation to maximally 200%-220% of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Changes in the rat brain 5-HT1A and 5-HT2 receptors after chronic administration of levoprotiline, (+)-oxaprotiline and other antidepressant drugs.

The effects of levoprotiline (LEV), a (-)-enantiomer of oxaprotiline (OXA) and a clinically effective antidepressant, on the binding parameters of hippocampal 5-HT1A and cortical 5-HT2 receptors of rats were compared with those of (+)-enantiomer of OXA ((+)-OXA), imipramine and mianserin. Both LEV and (+)-OXA displayed in vitro some affinity for 5-HT1A receptors labelled with [3H]-8-OH-DPAT, and for 5-HT2 receptors labelled with [3H]-ketanserin. Repeated administration of LEV, for 14 days led to a marked increase in the number of 5-HT1A binding sites in the rat hippocampus, with no change in the KD values. (+)-OXA, imipramine and mianserin produced similar effects on 5-HT1A binding parameters. The number of 5-HT2 receptors was increased after two weeks of LEV administration, not altered after (+)-OXA, and decreased after imipramine or mianserin. The number of [3H]-ketanserin binding sites was decreased after four weeks of (+)-OXA administration, but not altered after LEV. The specific binding of [3H]-ketanserin in the rat cerebral cortex was decreased after repeated treatment with LEV and (+)-OXA (ex vivo). In competition studies the affinity of serotonin for [3H]-ketanserin binding sites was decreased in LEV- and increased in (+)-OXA-treated rats. The results suggest that LEV similarly to other antidepressants increases the number of 5-HT1A receptors, however without common alteration in 5-HT2 receptor number and function.

Animals↗

PubMed1992

Peripheral 5-carboxamidotryptamine induces hindlimb scratching by stimulating 5-HT1A receptors in rats.

Treatment of rats with 5-carboxamidotryptamine (5-CT) or 5-methoxy-tryptamine (5-MeOT) induces a hindlimb scratch response. These compounds have high affinity for 5-HT1A and 5-HT1D receptors. The selective 5-HT1A receptor agonist N,N-dipropyl-5-CT (DP-5-CT) also induced hindlimb scratching while the selective 5-HT1D receptor agonist, sumatriptan, did not. 5-CT-induced hindlimb scratching was inhibited dose-dependently by several 5-HT1A antagonists (BMY 7378, NAN-190, MDL 73005EF and pindobind-5-HT1A) as well as the non-selective 5-HT antagonist, methiothepin. Pretreatment of rats with the serotonin (5-HT) synthesis inhibitor, p-chlorophenylalanine (PCPA) or the 5-HT depleting agent, reserpine, markedly attenuated 5-CT-induced hindlimb scratching. These data suggest that hindlimb scratching induced by 5-HT agonists may not be centrally mediated but rather may be mediated by a neuronal 5-HT1A receptor localized outside the blood-brain barrier.

5-Methoxytryptamine↗

PubMed1992

Neurochemical effects of 5-HT1 receptor ligands in pigeons.

Pigeon cerebrospinal fluid was assayed for 5-HT (5-hydroxytryptamine) and catecholamine metabolites after systemic drug injection. The 5-HT1-like receptor agonists 8-hydroxy-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole (RU 24969), 1-(m-trifluoromethylphenyl)piperazine (TFMPP), and 1-(3-chlorphenyl)piperazine (mCPP) decreased levels of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) without altering other metabolites. 5-HIAA decreases occurred at doses of 8-OH-DPAT and RU 24969 that have anti-conflict effects in pigeons, whereas TFMPP and mCPP decreased 5-HIAA only at behaviorally disruptive doses. The novel compound 1-(2-methoxyphenyl)-1-(4-(2-phthalimido)butyl)piperazine (NAN-190), a putative 5-HT1A receptor antagonist, did not affect 5-HIAA, but attenuated the decreases produced by the agonists. NAN-190 and the alpha 1-adrenoceptor antagonist prazosin increased levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol and had additive effects when co-administered. The rank order of potency in inhibiting [3H]8-OH-DPAT binding in pigeon cerebrum was 8-OH-DPAT = RU 24969 > NAN-190 >> mCPP > TFMPP. The results support suggestions that decreased 5-HT neurotransmission underlies the anxiolytic-like effects of 5-HT1A receptor agonists in pigeons.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMedDate not supplied

Cortical and septal responses to dorsal raphe nucleus stimulation in the rat: long-term clomipramine actions.

In cerebral cortex and lateral septal nuclei different serotonergic receptor subtypes coexist, thus a different action on neuronal firing may be expected depending on the receptor activated. Dorsal raphe nucleus stimulation produced an increased rate of firing in cortical layer V, and in lateral septal nuclei. However, firing rate in cortical layer VI remained unchanged after stimulating the dorsal raphe nucleus. Clomipramine is a tricyclic which exerts its main actions on serotonergic receptors, and long-term treatment with this antidepressant produced a selective increased firing rate in lateral septal neurons, but not in cortical neurons. From an electrophysiological point of view, it is concluded that the excitatory actions on firing rate elicited by dorsal raphe nucleus stimulation or clomipramine treatment are mediated by 5-HT2 receptor subtype activation which is likely to be acting as a 5-HT1A modulator in such places where both receptor subtypes coexist.

Action Potentials↗

PubMed1992

Effects of 5-HT1A receptor agonists on the circadian rhythm of wheel-running activity in hamsters.

The effects of 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), buspirone and ipsapirone on wheel-running activity in hamsters were investigated in comparison with those of GABAA receptor agonist muscimol and benzodiazepine triazolam. Intraperitoneal administration of 8-OH-DPAT, buspirone, ipsapirone, muscimol and triazolam at circadian time (CT) 8 (CT 12; onset of activity) induced a significant phase advance of wheel-running activity under constant light conditions. However, administration of these drugs at other CT points did not induce phase changes. The administration of trifluoromethylphenylpiperazine (TFMPP), a 5-HT1B receptor agonist, at CT8 produced a small phase advance. The phase advance induced by 8-OH-DPAT was blocked by pretreatment with (-)-pindolol, a 5-HT1A receptor antagonist. In addition, 8-OH-DPAT, buspirone and SM3997 accelerated the rate of re-entrainment to an 8-h phase advance in the light-dark cycle. These observations suggest that 5-HT1A receptors in the brain participate in the regulation of the circadian rhythm of wheel-running activity in hamsters.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

S 14671: a naphtylpiperazine 5-hydroxytryptamine1A agonist of exceptional potency and high efficacy possessing antagonist activity at 5-hydroxytryptamine1C/2 receptors.

The interaction at 5-hydroxytryptamine (5-HT) receptors of the novel naphtylpiperazine, S 14671 (1-[2-(2-thenoylamino)ethyl]-4[1-(7- methoxynaphtyl)]piperazine), was compared to that of the 5-HT1A ligands, 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), WY 50,324 [N-(29(4-(2-pyrimidinyl)-1-piperazinyl)ethyl)tricyclo(3.3.1.1(3,7) )- decane-1-carboxamide], (+)-flesinoxan, buspirone and BMY 7378 [(8-[2-[4-(2-methoxyphenyl)- 1-piperazinyl]ethyl]-8-azaspirol[-4-]-decane-7,9-dione 2HCl]. S 14671 showed a very high affinity for 5-HT1A sites (pKi, 9.3) as compared to the reference ligands (pKi values, 9.2, 8.7, 8.7, 7.9 and 8.7, respectively). S 14671 bound in an apparently competitive manner and, in distinction to the reference compounds, possessed a Hill Coefficient (1.4) significantly superior to 1. Although showing low affinity at 5-HT1B and 5-HT3 sites, S 14671 displayed significant affinity at both 5-HT1C and 5-HT2 sites; pKi, 7.8 in each case. Furthermore, S 14671 acted as an antagonist of 5-HT-stimulated phosphoinositide turnover in rat choroid plexus (5-HT1C) and cortex (5-HT2). In vivo, upon s.c. administration, S 14671 acted as a high efficacy agonist in models of 5-HT1A receptor-mediated activity: induction of flat-body posture, spontaneous tail-flicks, hypothermia and corticosterone secretion and inhibition of morphine-induced antinociception. In every test, S 14671 was the most potent compound: it was active at doses as low as 5 micrograms/kg s.c. Relative potency across all tests was S 14671 greater than 8-OH-DPAT greater than WY 50,324 greater than (+)-flesinoxan greater than buspirone with BMY 7378 too weak for comparison to be meaningful. The action of S 14671 in 5-HT1A tests was blocked by BMY 7378 and the 5-HT1A antagonist, (-)-alprenolol, but unaffected by the 5-HT1C/2 antagonist, ritanserin, and the 5-HT3 antagonist, ondansetron. Activation of postsynaptic 5-HT1A receptors was confirmed in 5,7-dihydroxytryptamine-lesioned rats, in which the potency of S 14671 to elicit spontaneous tail-flicks was potentiated. Activation of presynaptic receptors was demonstrated by inhibition of the electrical activity of the dorsal raphe nucleus with the following order of relative potency: S 14671 greater than 8-OH-DPAT greater than WY 50,324 greater than BMY 7378 greater than buspirone. Spiperone, which acts as a pure 5-HT1A antagonist at raphe 5-HT1A receptors, blocked the action of S 14671. In conclusion, S 14671 is a structurally novel ligand manifesting high efficacy and exceptional potency at both pre- and postsynaptic 5-HT1A receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

Novel indolodioxanes with antihypertensive effects: potent ligands for the 5-HT1A receptor.

The synthesis and biological evaluation of a new family of tricyclic indolodioxanes is described. These compounds all contain the 2,3-dihydro-7H-1,4-dioxino[2,3-e]indole nucleus and bear substituents at the 2 and/or 8 positions. Thirteen members of this class were prepared and shown to be potent ligands for the 5-HT1A receptor, with several compounds displaying subnanomolar inhibition constants. These compounds also bind to the dopamine D-2 receptor, but generally with higher inhibition constants than those for 5-HT1A. Certain members of this novel structural class show in vivo activity in the mouse hypothermia assay. One of these compounds, U-86192A, has been shown to have antihypertensive effects in the cat, completely eliminating sympathetic nerve discharge at 1 mg/kg iv and lowering mean arterial pressure to 50% pretreatment levels. These effects can be reversed by the administration of spiperone, indicating that U-86192A is acting via a central serotonergic mechanism.

Animals↗

PubMed1992

N-methyl-D-aspartate receptor antagonists counteract the long lasting 5-HT1A receptor-induced attenuation of postsynaptic responses in the rat in vivo.

The effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists dizocilpine and phenycyclidine, the competitive NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the antagonist at the glycine modulatory site of the NMDA receptor, 3-amino-1-hydroxy-2-pyrrolidone (HA-966) on the long lasting attenuation of some post-synaptic 5-HT1A receptor-mediated responses in rats (increased corticosterone secretion and inhibition of the cage leaving response) produced by a single injection of the 5-hydroxytryptamine1A (5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was studied. It was found that these antagonists counteracted the attenuation of these responses at dose levels known to block the NMDA receptor-ion channel complex in vivo. It is concluded that the long lasting attenuation of postsynaptic responses after a 5-HT1A receptor agonist is initiated through stimulation of glutamate NMDA receptors indicating a functional interaction between the 5-HT and glutamate systems in at least two different models.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

Characterization of a novel 5-HT4 receptor antagonist of the azabicycloalkyl benzimidazolone class: DAU 6285.

Three chemical classes of serotonin 5-HT4 receptor agonists have been identified so far: 5-substituted indoles (e.g. 5-HT), benzamides (e.g. renzapride) and benzimidazolones (e.g. BIMU 8). In a search for 5-HT4 receptor antagonists, we have discovered that the benzimidazolone derivative DAU 6285 (for structure see text), is 3-5 times more potent than tropisetron in blocking 5-HT, renzapride and BIMU 8 induced stimulation of adenylate cyclase activity in mouse embryo colliculi neurons. Schild plot analysis yielded Ki values of 220, 181 and 255 nmol/l, respectively. In addition, DAU 6285 showed poor activity as a 5-HT3 receptor ligand with respect to tropisetron, as demonstrated by in vitro binding studies (Ki, 322 vs 2.8 nmol/l) and by its antagonistic activity in the Bezold-Jarisch reflex test (ID50, 231 vs 0.5 micrograms/kg, i.v.). No significant binding (Ki greater than 10 mumol/l) of DAU 6285 to serotonergic 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, and 5-HT2 receptors as well as to adrenergic alpha 1, alpha 2, dopaminergic D1, D2 or muscarinic M1-M3 receptor subtypes was found. The data indicate that DAU 6285 has a somewhat higher affinity than tropisetron for 5-HT4 receptors, a property confirmed in functional tests, and much lower affinity than tropisetron for 5-HT3 receptors. The compound represents a new interesting tool for investigating the pharmacological and physiological properties of 5-HT4 receptors.

Animals↗

PubMed1992

5-HT1-like receptor mediated changes in porcine carotid haemodynamics: are 5-HT1D receptors involved?

5-Hydroxytryptamine (5-HT) reduces porcine arteriovenous shunting in the carotid vascular bed by stimulation of both 5-HT1-like and 5-HT2 receptors and increases capillary flow to some tissues, like the skin and ears, by different 5-HT1-like receptors. In view of the heterogeneous nature of the 5-HT1-like receptors and the relative selectivity for the 5-HT1D binding sites of sumatriptan, which also reduces porcine arteriovenous shunting and slightly increases capillary blood flow towards skin and ears by 5-HT1-like receptors, we have attempted to determine whether one or both of these carotid 5-HT1-like receptors belong to the 5-HT1D subtype. Pentobarbitone anaesthetized pigs, subjected to bilateral cervical vagosympathectomy, received either 5-HT (2 micrograms.kg-1.min-1) in the carotid artery or cumulative i.v. doses of sumatriptan (10, 30, 100 and 300 micrograms.kg-1). Their effect on the total carotid blood flow and its distribution into capillary and arteriovenous anastomotic parts was determined with radioactive microspheres. The effect of metergoline (1 mg.kg-1), a substance with a very high affinity for the 5-HT1D receptor as well as for the 5-HT1A, 5-HT1B, 5-HT1C and 5-HT2 receptors, was studied on the responses to 5-HT and sumatriptan. Both 5-HT and sumatriptan reduced carotid arteriovenous anastomotic blood flow. 5-HT and, to a lesser extent, sumatriptan also increased capillary blood flow towards some tissues. Metergoline by itself did not affect the distribution of porcine carotid blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Effect of established and putative anxiolytics on extracellular 5-HT and 5-HIAA in the ventral hippocampus of rats during behaviour on the elevated X-maze.

One of the proposed mechanisms of action for the anxiolytic effects of the benzodiazepines is via a decrease in central serotonergic neurotransmission. The aim of this study was to combine in vivo microdialysis in the rat with behaviour on the elevated X-maze to determine changes in 5-HT release in the ventral hippocampus with concomitant measurement of behaviour. Twenty minutes exposure to the elevated X-maze resulted in an increase in extracellular 5-HT in the ventral hippocampus with no change in extracellular 5-HIAA. Restricting the rat to either the open or the closed arms produced an increase in extracellular 5-HT, however the increase in 5-HT when restricted to the open arms was not significantly greater than that on the closed arms. Forty minutes pretreatment with diazepam (2.5 mg kg-1 IP) significantly inhibited the increase in extracellular 5-HT in the ventral hippocampus and had an anxiolytic profile over 5 min and 20 min exposures of the rats to the X-maze. Diazepam had no effect on basal 5-HT levels before exposure to the X-maze but reduced extracellular 5-HT levels when the animal was returned to the holding cage. Forty minutes pretreatment with the .5-HT1A receptor partial agonist ipsapirone (1 mg kg-1 IP) significantly inhibited the increase in extracellular 5-HT in the ventral hippocampus but did not produce behaviour different from vehicle controls after 5 or 20 min periods on the X-maze.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1992

Effect of the selective lesion of serotoninergic neurons on the regional distribution of 5-HT1A receptor mRNA in the rat brain.

The effects of the selective lesion of serotoninergic neurons by an intra-raphe administration of 5,7-dihydroxytryptamine on the 5-HT1A receptor protein and the 5-HT1A receptor mRNA were examined in various regions of the rat brain using specific antibodies and an antisense riboprobe, respectively. Twenty one days after the treatment, the 5-HT1A receptor protein was no longer detected within the dorsal raphe nucleus but was still present in the hippocampus and entorhinal cortex. Quantitative in situ hybridization showed an 85% decrease in the levels of 5-HT1A receptor mRNA within the dorsal raphe nucleus, but no significant change in the hippocampus, interpeduncular nucleus and entorhinal cortex of 5,7-dihydroxytryptamine-treated rats. These data demonstrate that 5-HT1A receptors are synthesized by serotoninergic neurons in the dorsal raphe nucleus, and by neurons located postsynaptically with regard to serotoninergic projections in other areas. The unchanged levels of 5-HT1A receptor mRNA in the hippocampus, interpeduncular nucleus and entorhinal cortex three weeks after the extensive lesion of serotoninergic neurons are consistent with the absence of 5-HT1A receptor up regulation already reported under this condition.

5,7-Dihydroxytryptamine↗

PubMed1992

[Effect of long-term feeding with tryptophan-free diet on the circadian rhythm in rats].

Effects of long-term feeding with tryptophan (TRP)-free diet on the free running periods of wheel-running rhythm and the central serotonergic neurotransmission were examined in male blinded rats. Long-term feeding with TRP-free diet did not change the periods of wheel-running rhythm calculated from chi 2 periodogram but disordered its pattern, which seemed to be due to masking or entrainment effects. On the other hand, long-term TRP-free diet decreased the concentrations of TRP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in all brain regions tested; frontal cortex, hippocampus, thalamus, hypothalamus and pons. The density of 5-HT1A receptor (3H-8-OH-DPAT) binding was significantly decreased in only frontal cortex, while no significant change was observed in the density of 5-HT2 receptor (3H-ketanserin) binding in all regions. Although the mechanism of down-regulation of 5-HT1A receptor in frontal cortex is obscure, it was confirmed that TRP-free diet decreased central 5-HT synthesis and 5-HT neurotransmission. This dysfunction of 5-HT neurotransmission by TRP-free diet is suggested to make the circadian rhythm pacemaker susceptible to subtle environmental factors by lowering its intensity.

Animals↗

PubMedDate not supplied

Pharmacological profile of a new 5-hydroxytryptamine2 receptor antagonist, DV-7028.

The pharmacological profile of DV-7028, a pyrido triazine derivative, showed that it is a potent and selective 5-hydroxytryptamine (5-HT)2 receptor antagonist. DV-7028 bound to 5-HT2 receptors in rat brain membranes with a Ki value of 22 nM and caused shifts to the right of the concentration-contraction curves to 5-HT in rat thoracic aorta and canine femoral arteries, which are attributed to activation of 5-HT2 receptors. The compound was highly active by oral administration (0.1-10 mg/kg) based on blockade of the 5-HT-induced pressor responses in pithed rats. In contrast, DV-7028 had no affinity for 5-HT1A, 5-HT1B and 5-HT1D receptors. The affinity of the compound was 14-26 times greater for the 5-HT2 receptors when compared to 5-HT1C, adrenergic alpha 1, dopamine D2 and histamine H1 receptors. In human platelets, DV-7028 attenuated the aggregation induced by collagen and inhibited the amplifying effect of 5-HT with collagen on platelet aggregation. Furthermore, a 10-day toxicity study revealed that DV-7028 was a safe compound which did not produce lethality at repeated oral doses of 800 mg/kg/day in rats. These results indicate that DV-7028 is a selective and potent 5-HT2 receptor antagonist which is orally active and safe.

Animals↗

PubMedDate not supplied

Structure-activity relationship studies of CNS agents. Part VII. The effect of the imidazole fragment in 2-substituted 1-[3-(4-aryl-1-piperazinyl)propyl]imidazoles on their interaction modes with 5-HT1A and 5-HT2 receptors.

The synthesis and the 5-HT1A and 5-HT2 receptor affinity of 2-substituted 1-[3-(4-aryl-1-piperazinyl)propyl]-imidazoles (1-8) has been described. It has been shown that both the N-3 imidazole atom and the N-1 piperazine one should be considered as possible protonation centers under physiological conditions. It has been found that the folded conformations of 1-8 exist predominantly in solution. Moreover, three different modes of interaction of the analyzed compounds with 5-HT1A and 5-HT2 receptor sites have been proposed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMedDate not supplied

Structure-activity relationship studies of CNS agents. Part VIII. Bulk tolerance around the protonation center of 4-substituted 1-(3-chlorophenyl)piperazines at 5-HT1A and 5-HT2 receptors.

The effect of a steric hindrance around the protonation center of the model 4-substituted 1-(3-chlorophenyl)-piperazines 1-9 and 11-14 on their affinity for 5-HT1A and 5-HT2 receptor sites was investigated. Additional evidence for hydrophobic interactions between the N-4 hydrocarbon substituents and 5-HT1A receptors has been presented. However, the hydrophobic forces play a minor role in stabilization of the bioactive complex with 5-HT2 receptors. It has also been found that even bulky substituents around the protonation center of 1-aryl-piperazines are well tolerated at both 5-HT1A and 5-HT2 sites.

Animals↗