No abstract available.
Hemodynamics* ; Ketanserin* ; Positive-Pressure Respiration* ; Pulmonary Embolism* ; Ventilation*

We evaluated the in vivo kinetics, distribution, and pharmacology of N-(4-[F] fluorornethylbenzyl)spiperone ([F]FMBS), a newly developed derivative of spiperone, as a potentially more selective #radiotrar.er for the dopamine (DA) Dz receptors. Mice received 1.9-3.7 MBq (1.8-3.6 nmol/kg) of [F]FMBS by tail vein injectivn. The time course and regional distribution of the tracer in brain were assessed. Blocking studies were carried out by intravenously preinjecting DA Dp receptor blockers (spiperone, butaclamol) as well as drugs with high affinity for DA Dr lSCH 23390), DA transporter (GBR 12909), and serotonin Sp (5-HTz) (ketanserin) sites. After injection of the tracer, the radioactivity in striatum increased steadily over time, resulting in a striatal-to-cerebellar ratio of 4.8 at 120 min postinjection. By contrast, the radioactivity in cerebellum, frontal cortex, and remaining cortex washed out rapidly. Preinjection of unlabe1ed FMBS (1 rng/kg) and spiperone (1 mg/kg) reduced [F] FMBS striatal-to-cerebellar ratio by 41Zo and 80Ya, respectively. (+)-Butaclamol(1 mg/kg) blocked 80Yo of the striatal [F]FMBS binding, while (-)-butaclamol (1 rng/kg) did not. Preinjection of SCH 23390 (1 mg/kg) and GBR 12909 (5 mg/kg) had no significant effect. On [""F]FMBS binding. Ketanserin (1 mg/kg), a ligand for the 5-H1g receptors, did not cause significant inhibition either in striatum, in frontal cortex, or the remaining cortex. The results demonstrate that [F]FMEtS labels DA Dz receptors selectively in vivo in the mouse brain. It may hold promise as a selective radiotracer for studying DA Dz receptors in vivo by PET.
Animals ; Brain ; Cerebellum ; Dopamine* ; Ketanserin ; Kinetics ; Mice ; Pharmacology ; Radioactivity ; Receptors, Dopamine D2* ; Serotonin ; Spiperone* ; Veins

To evaluate the antihypertensive effects of serotonin antagonist, ketanserin, a daily dosage of 10~40mg (18.9+/-6.8 mean+/-SE) was administered to 22 patients with essential hypertension and aged 55??1 years (64+/-7.7 mean+/-SE) for 12 weeks. After 12 weeks of ketanserin treatment mean blood pressure decreased from 177.9+/-11.9 to 15.7+/-15.3mmHg in systole and from 104.2+/-7.4 to 88.4+/-7.9mmHg in diastole (P<0.001). There was no significant change in heart rates with ketanserin treatment. The antihypertensive treatment with ketanserin was effective in 18 patients(81.8%) and ineffective in 4 patients (18.2%). Adverse reactions such as drowsiness (8.7%), edama (4.3%) and weakness (4.3%) were noted, but all were mild and transient. This results suggest that ketanserin is an effective and safe antihypersive agent in the treatment of essential hyperension.
Aging* ; Blood Pressure ; Diastole ; Heart Rate ; Humans ; Hypertension* ; Ketanserin* ; Serotonin ; Sleep Stages ; Systole

PURPOSE: The aim of this study was to assess the potential involvement of a specific subtype of 5-hydroxytryptamine (5-HT), 5HT(2) receptors in neurally-induced contractions of the human detrusor. METHODS: Contractile responses to electrical field stimulation (EFS) were examined in human isolated urinary bladder muscle strips. The potentiation of EFS-induced detrusor contraction was examined by adding cumulative concentrations of a 5-HT and 5-HT(2) receptor agonist, α-methyl-serotonin (α-Me-5-HT) (1nM–100μM) in the presence or absence of a 5-HT₂ antagonist, ketanserin (5-HT(2A)>5-HT(2C)) or naftopidil (5-HT(2B)>5-HT(2A)) (0.3–3μM). RESULTS: 5-HT and α-Me-5-HT potentiated EFS-induced contraction with a maximal effect (E(max)) of 37.6% and 38.6%, respectively, and with pEC(50) (negative logarithm of the concentration required for a half-maximal response to an agonist) values of 8.3 and 6.8, respectively. Neither ketanserin nor naftopidil at any concentration produced a rightward displacement of the α-Me-5-HT concentration response curve. Instead, the E(max) of α-Me-5-HT increased in the presence of ketanserin at 0.3–1μM and in the presence of naftopidil at 1μM to 51% and 56%, respectively, while the E(max) in the presence of vehicle alone was 36%. The highest concentration (3μM) of either drug, however, fully reversed the enhancement. CONCLUSIONS: The potentiating effect of α-Me-5-HT on neurally-induced contraction of human urinary bladder muscle strips was not found to be mediated via any 5-HT(2) receptor subtypes. The underlying mechanism for the enhancement of the α-Me-5-HT potentiating effect on detrusor contractility by ketanserin and naftopidil remains unknown; however, our results suggest that these drugs may be useful for treating contractile dysfunction of the detrusor, as manifested in conditions such as underactive bladder.
Humans* ; Ketanserin* ; Prostatism ; Receptors, Adrenergic, alpha-1 ; Receptors, Serotonin ; Serotonin ; Urinary Bladder Neck Obstruction ; Urinary Bladder*

Recent reports claimed that glucosylsphingosine (GS) is highly accumulated and specifically evoking itch-scratch responses in the skins of atopic dermatitis (AD) patients. However, it was unclear how GS can trigger itch-scratch responses, since there were no known molecular singling pathways revealed yet. In the present study, it was verified for the first time that GS can activate mouse serotonin receptor 2a (mHtr2a) and 2b (mHtr2b), but not 2c (mHtr2c) that are expressed in HEK293T cells. Specifically, effects of GS on all mouse serotonin receptor 2 subfamily were evaluated by calcium imaging techniques. The GS-induced intracellular calcium increase was dose-dependent, and antagonists such as ketanserin (Htr2a antagonist) and RS-127445 (Htr2b antagonist) significantly blocked the GS-induced responses. Moreover, the proposed GS-induced responses appear to be mediated by phospholipase C (PLC), since pretreatment of a PLC inhibitor U-73122 abolished the GS-induced responses. Additionally, the GS-induced calcium influx is probably mediated by endogenous TRPC ion channels in HEK293T cells, since pretreatment of SKF-96365, an inhibitor for TRPC, significantly suppressed GS-induced response. In conclusion, the present study revealed for the first time that GS can stimulate mHtr2a and mHtr2b to induce calcium influx, by utilizing PLC-dependent pathway afterwards. Considering that GS is regarded as a pruritogen in AD, the present study implicates a novel GS-induced itch signaling pathway.
Animals ; Calcium ; Dermatitis, Atopic ; Humans ; Ion Channels ; Ketanserin ; Mice ; Serotonin* ; Skin ; Type C Phospholipases

The effect of ketanserin, serotonin antagonist, among 19 korean patients over 55 years with essential hypertension was assessed in an open clinical trial for three months. patients were given Ketanserin 20mg bid with monthly follow-up visits. Mean values of systolic/diastolic blood pressures fell from 169+/-17/104+/-10mmHg to 155+/-14/94+/-9mmHg at 2 weeks(p<0.01) and to 147+/-10/87+/-6mmHg at end of treatment 12 weeks after(p<0.001). There was no significant change in heart rate. Transient mild side effects were observed in 5 patients. We conclude that Ketanserin is an effective and safe drug for the treatment of elderly hypertensives.
Aged ; Follow-Up Studies ; Heart Rate ; Humans ; Hypertension* ; Ketanserin* ; Middle Aged* ; Serotonin

Central tryptaminergic system has been shown to play an important role in the regulation of renal function: 5-HT-1 (5-hydroxytryptamine-1) receptors might seem to mediate the diuresis and natriuresis, whereas the 5-HT-2 and 5-HT-3 receptors mediate the antidiuretic and antinatriuretic effects. This study attempted to delineate the role of central 5-HT-1A subtype in the regulation of rabbit renal function by observing the renal effects of intracerebroventricularly(icv)-administered PAPP (p-aminophenylethyl-m-trifluoromethylphenyl piperazine, LY165163), a selective agonist of 5-HT-1A receptors. PAPP in doses ranging from 40 to 350 microgram/kg icv induced significantly diuresis, natriuresis, and kaliuresis, along with increased renal perfusion and glomerular filtration. Systemic blood pressure was also increased. Free water reabsorption (T-cH-2O), a measure of ADH (antidiuretic hormone) secretion, was increased also. Intravenous 350 microgram/kg of PAPP elicited antidiuresis and antinatriuresis together with decreased blood pressure, thus indicating that the effects of icv PAPP were brought about through the central mechanisms, not by direct peripheral effects of the drug on kidney. Ketanserin, a selective 5-HT-2 antagonist, 40 microgram/kg icv, did not affect the renal effects of the icv PAPP. Methysergide, a non-selective 5-HT-1 antagonist, also did not block the renal functional responses by the icv PAPP. NAN-190, a 5-HT-1A antagonist, also did not antagonized the renal action of the icv PAPP. However the increased free water reabsorption was abolished by both methysergide or ketanserin pretreatment. The increments of blood pressure by icv PAPP was blocked only by NAN-190 pretreatment. These observations suggest that the central 5-HT-1A receptor might be involved in the central regulation of rabbit renal function by exerting the diuretic and natriuretic influences.
Blood Pressure ; Diuresis ; Filtration ; Ketanserin ; Kidney ; Methysergide ; Natriuresis ; Perfusion ; Rabbits* ; Water

The aim of this study was to investigate the role of the 5-HT receptors in acetylcholine (ACh) release from the striatum. Slices from the rat striatum and synaptosomes were incubated with [3H]-choline and the release of the labelled products was evoked by electrical (3 Hz, 2 ms, 5 V/cm, rectangular pulses, 2 min) and potassium-stimulation (25 mM), respectively, and the influence of various serotonergic drugs on the evoked tritium outflows was investigated. Serotonin decreased the electrically-evoked ACh release in striatum in a concentration-dependent manner without the change of basal release. In hippocampal and entorhinal cortical slices, serotonin did not affect the evoked and basal release of ACh, but, at large dose (30 microM) decreased the evoked ACh release in hippocampus. 2,5-Dimethoxy-4-iodoamphetamine (DOI), a specific 5-HT 2A/2C agonist, decreased evoked ACh release in the striatum. CGS-12066A (5-HT 1B agonist), m-chlorophenyl-biguanide (5-HT 3 agonist) and 5-[(dimethyl -amino)methyl]-3-(1-methyl-1H-indol-3-yl)-1,2,4-oxadiazole (5-HT 3 antagonist) did not affect the evoked and basal ACh release in all tissues. Ritanserin, a specific 5-HT 2A/2C antagonist, blocked the inhibitory effects of serotonin and DOI, whereas, ketanserin, an another type of specific 5-HT 2A/2C antagonist did not affect the inhibitory effects of serotonin and DOI. In striatal synaptosomal preparation, serotonin and DOI did not affect the K +-evoked ACh release. These findings suggest that ritanserin-sensitive 5-HT 2A/2C receptors located in the soma and/or axons of the striatal cholinergic neurons play a important role in ACh release.
Acetylcholine* ; Animals ; Axons ; Carisoprodol ; Cholinergic Neurons ; Hippocampus ; Ketanserin ; Rats* ; Receptors, Serotonin* ; Ritanserin ; Serotonin Agents ; Serotonin* ; Synaptosomes ; Tritium

It was aimed to investigate the effect of 5-HT2C receptor modulation on the rat behavioral responses induced by 1-(m-chlorophenyl) piperazine(mCPP), a major metabolite of trazodone. The animal activities(ambulation, stereotypy and total activity) were measured for 3 hours following mCPP administration, using an animal activity meter which accumulates the frequency of light beam interruption. mCPP(1-10 mg / kg, i.p.) induced dose-dependent decreases in ambulation and stereotypy, consequently leading to hypoactivity. The hypoactivity induced by mCPP(1mg / kg, i.p.) was significantly inhibited by pretreatment with mianserin(1mg / kg, i.p.), an antagonist with high affinity for 5-HT2C receptor, whereas pretreatment with 5-HT2 antagonists, ketanserin and ritanserin(1mg / kg, i.p., respectively) was without effect. Furthermore, long-term pretreatment with imipramine(10mg / kg, i.p., b.i.d. for 2 weeks) markedly attenuated the mCPP-induced hypoactivity. Mianserin and imipramine in the absence of mCPP did not increase the animal activity. Taken together, these results indicate that the mCPP-induced hypoactivity is mediated by 5-HT2C receptor, and that selective 5-HT2C antagonists and down regulation of 5-HT2C receptor might be useful for inhibiting the mCPP-induced hypoactivity.
Animals ; Down-Regulation ; Imipramine ; Ketanserin ; Mianserin ; Rats ; Receptor, Serotonin, 5-HT2C* ; Serotonin 5-HT2 Receptor Antagonists ; Trazodone ; Walking

BACKGROUNDKetanserin (KT), a selective serotonin (5-HT) 2-receptor antagonist, reduces peripheral blood pressure by blocking the activation of peripheral 5-HT receptors. In this study electrophysiological method was used to investigate the effect of KT and potassium ion on Kv1.3 potassium channels and explore the role of blocker KT in the alteration of channel kinetics contributing to the potassium ion imbalances.

METHODSKv1.3 channels were expressed in xenopus oocytes, and currents were measured using the two-microelectrode voltage-clamp technique.

RESULTSKCl made a left shift of activation and an inactivation curve of Kv1.3 current and accelerated the activation and inactivation time constant. High extracellular [K(+)] attenuated the blockade effect of KT on Kv1.3 channels. In the presence of KT and KCl the activation and inactivation time constants were not influenced significantly no matter what was administered first. KT did not significantly inhibit Kv1.3 current induced by tetraethylammonium (TEA).

CONCLUSIONSKT is a weak blocker of Kv1.3 channels at different concentrations of extracellular potassium and binds to the intracellular side of the channel pore. The inhibitor KT of ion channels is not fully effective in clinical use because of high [K(+)](o) and other electrolyte disorders.

Animals ; Electrophysiology ; Female ; Ketanserin ; pharmacology ; Kv1.3 Potassium Channel ; drug effects ; metabolism ; Oocytes ; Patch-Clamp Techniques ; Potassium ; pharmacology ; Serotonin Antagonists ; pharmacology ; Xenopus laevis