bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of [Nphe1]nociceptin(1‐13)NH2, a new selective nociceptin receptor antagonist
Authors: Calo' Girolamo , Guerrini Remo , Bigoni Raffaella , Rizzi Anna , Marzola Giuliano , Okawa Hirobumi , Bianchi Clementina , Lambert David G , Salvadori Severo , Regoli Domenico 
Published: January 2005

Nociceptin (orphanin FQ) is a novel neuropeptide capable of inducing a variety of biological actions via activation of a specific G‐protein coupled receptor. However, the lack of a selective nociceptin receptor antagonist has hampered our understanding of nociceptin actions and the role of this peptide in pathophysiological states. As part of a broader programme of research, geared to the identification and characterization of nociceptin receptor ligands, we report that the novel peptide [Nphe1]nociceptin(1‐13)NH2 acts as the first truly selective and competitive nociceptin receptor antagonist and is devoid of any residual agonist activity.
[Nphe1]nociceptin(1‐13)NH2 binds selectively to recombinant nociceptin receptors expressed in Chinese hamster ovary (CHO) cells (pKi 8.4) and competitively antagonizes the inhibitory effects of nociceptin (i) on cyclic AMP accumulation in CHO cells (pA2 6.0) and (ii) on electrically evoked contractions in isolated tissues of the mouse, rat and guinea‐pig with pA2 values ranging from 6.0 to 6.4.
[Nphe1]nociceptin(1‐13)NH2 is also active in vivo, where it prevents the pronociceptive and antimorphine actions of intracerebroventricularly applied nociceptin, measured in the mouse tail withdrawal assay. Moreover, [Nphe1]nociceptin(1‐13)NH2 produces per se a dose dependent, naloxone resistant antinociceptive action and, at relatively low doses, potentiates morphine‐induced analgesia.
Collectively our data indicate that [Nphe1]nociceptin(1‐13)NH2, acting as a nociceptin receptor antagonist, may be the prototype of a new class of analgesics.

British Journal of Pharmacology (2000) 129, 1183–1193; doi:10.1038/sj.bjp.0703169
Neuroleptics ameliorate phencyclidine‐induced impairments of short‐term memory
Authors: Schroeder Ulrike , Schroeder Helmut , Schwegler Herbert , Sabel Bernhard A 
Published: January 2005

Phencyclidine (PCP), a non‐competitive NMDA‐receptor antagonist, is able to induce schizophrenia‐like symptoms in animals and in humans. It is known that schizophrenic patients have deficits in memory processes.
Therefore, it was investigated whether subchronic pulsatile or continuous application of 5.0 mg kg−1 PCP over 5 days induce short‐term memory deficits in holeboard learning and the action of two different neuroleptics on this behavioural test.
First, an impairment in the holeboard task was described when the animals were tested 24 h after the last application but not after 15 min or 1 h after the last injection. Secondly, the influence of haloperidol and risperidone on the PCP‐induced short‐term memory changes was tested.
The combined application of PCP and risperidone led to a complete antagonism of the short‐term deficits, but the combined treatment with haloperidol was accompanied by a partial abolishment of the PCP‐induced deficits.
PCP led to an upregulation of the glutamate binding sites in striatum and nucleus accumbens whereas the D2 binding sites were reduced in striatum. The D1 binding sites seem to be unchanged. The receptor protein expression of glutamate receptors mGluR1, GluR2, GluR5/7 and NMDAR1 were not modified in response to PCP treatment.
The determination of a subpopulation of GABAergic interneurons shows a decrease of the cells within the CA3 of the hippocampal formation.
These findings indicate that PCP induced impairments in short term memory can be detected by holeboard learning and may provide an interesting tool for the search of new neuroleptics.

British Journal of Pharmacology (2000) 130, 33–40; doi:10.1038/sj.bjp.0703171
Role of endothelial cell hyperpolarization in EDHF‐mediated responses in the guinea‐pig carotid artery
Authors: Quignard J ‐F , Félétou M , Edwards G , Duhault J , Weston A H , Vanhoutte P M 
Published: January 2005

Experiments were performed to identify the potassium channels involved in the acetylcholine‐induced endothelium‐dependent hyperpolarization of the guinea‐pig internal carotid artery. Smooth muscle and endothelial cell membrane potentials were recorded in isolated arteries with intracellular microelectrodes. Potassium currents were recorded in freshly‐dissociated smooth muscle cells using patch clamp techniques.
In single myocytes, iberiotoxin (0.1 μM)‐, charybdotoxin (0.1 μM)‐, apamin (0.5 μM)‐ and 4‐aminopyridine (5 mM)‐sensitive potassium currents were identified indicating the presence of large‐ and small‐conductance calcium‐sensitive potassium channels (BKCa and SKCa) as well as voltage‐dependent potassium channels (KV). Charybdotoxin and iberiotoxin inhibited the same population of BKCa but a conductance specifically sensitive to the combination of charybdotoxin plus apamin could not be detected. 4‐aminopyridine (0.1–25 mM) induced a concentration‐dependent inhibition of KV without affecting the iberiotoxin‐ or the apamin‐sensitive currents.
In isolated arteries, both the endothelium‐dependent hyperpolarization of smooth muscle and the hyperpolarization of endothelial cells induced by acetylcholine or by substance P were inhibited by 5 mM 4‐aminopyridine.
These results indicate that in the vascular smooth muscle cells of the guinea‐pig carotid artery, a conductance specifically sensitive to the combination of charybdotoxin plus apamin could not be detected, comforting the hypothesis that the combination of these two toxins should act on the endothelial cells. Furthermore, the inhibition by 4‐aminopyridine of both smooth muscle and endothelial hyperpolarizations, suggests that in order to observe an endothelium‐dependent hyperpolarization of the vascular smooth muscle cells, the activation of endothelial potassium channels is likely to be required.

British Journal of Pharmacology (2000) 129, 1103–1112; doi:10.1038/sj.bjp.0703175
Influence of bilirubin and other antioxidants on nitrergic relaxation in the pig gastric fundus
Authors: Colpaert E E , Lefebvre R A 
Published: January 2005

The influence of several antioxidants (bilirubin, urate, ascorbate, α‐tocopherol, glutathione (GSH), Cu/Zn superoxide dismutase (SOD) and the manganese SOD mimic EUK‐8) on nitrergic relaxations induced by either exogenous nitric oxide (NO; 10−5 M) or electrical field stimulation (4 Hz; 10 s and 3 min) was studied in the pig gastric fundus.
Ascorbate (5×10−4 M), α‐tocopherol (4×10−4 M), SOD (300–1000 u ml−1) and EUK‐8 (3×10−4 M) did not influence the relaxations to exogenous NO. In the presence of GSH (5×10−4 M), the short‐lasting relaxation to NO became biphasic, potentiated and prolonged. Urate (4×10−4 M) and bilirubin (2×10−4 M) also potentiated the relaxant effect of NO. None of the antioxidants influenced the electrically evoked relaxations.
6‐Anilino‐5,8‐quinolinedione (LY83583; 10−5 M) had no influence on nitrergic nerve stimulation but nearly abolished the relaxant response to exogenous NO. Urate and GSH completely prevented this inhibitory effect, while it was partially reversed by SOD and bilirubin. Ascorbate, α‐tocopherol and EUK‐8 were without effect.
Hydroquinone (10−4 M) did not affect the electrically induced nitrergic relaxations, but markedly reduced NO‐induced relaxations. The inhibition of exogenous NO by hydroquinone was completely prevented by urate and GSH. SOD and ascorbate afforded partial protection, while bilirubin, EUK‐8 and α‐tocopherol were ineffective.
Hydroxocobalamin (10−4 M) inhibited relaxations to NO by 50%, but not the electrically induced responses. Full protection versus this inhibitory effect was obtained with urate, GSH and α‐tocopherol.
These results strengthen the hypothesis that several endogenous antioxidant defense mechanisms, enzymatic as well as non‐enzymatic, might play a role in the nitrergic neurotransmission process.

British Journal of Pharmacology (2000) 129, 1201–1211; doi:10.1038/sj.bjp.0703176
Beta‐3 adrenergic stimulation of L‐Type Ca2+ channels in rat portal vein myocytes
Authors: Viard Patricia , Macrez Nathalie , Coussin Frédéric , Morel Jean‐Luc , Mironneau Jean 
Published: January 2005

The effects of β3‐adrenergic stimulation were studied on the L‐type Ca2+ channel in single myocytes from rat portal vein using the whole‐cell mode of the patch‐clamp technique.
Reverse transcription‐polymerase chain reaction showed that β1‐, β2‐ and β3‐adrenoceptor subtypes were expressed in rat portal vein myocytes. Application of both propranolol (a non‐selective β1‐ and β2‐adrenoceptor antagonist) and SR59230A (a β3‐adrenoceptor antagonist) were needed to inhibit the isoprenaline‐induced increase in L‐type Ca2+ channel current.
L‐type Ca2+ channels were stimulated by CGP12177A (a β3‐adrenoceptor agonist with potent β1‐ and β2‐adrenoceptor antagonist property) in a manner similar to that of isoprenaline. The CGP12177A‐induced stimulation of Ca2+ channel current was blocked by SR59230A, cyclic AMP‐dependent protein kinase inhibitors, H‐89 and Rp 8‐Br‐cyclic AMPs, but was unaffected by protein kinase C inhibitors, GF109203X and 19‐31 peptide. This stimulation was mimicked by forskolin and 8‐Br‐cyclic AMP. In the presence of okadaic acid (a phosphatase inhibitor), the β3‐adrenoceptor‐induced stimulation was maintained after withdrawal of the agonist.
The β3‐adrenoceptor stimulation of L‐type Ca2+ channels was blocked by a pretreatment with cholera toxin and by the intracellular application of an anti‐Gαs antibody. This stimulation was unaffected by intracellular infusion of an anti‐Gβcom antibody and a βARK1 peptide.
These results show that activation of β3‐adrenoceptors stimulates L‐type Ca2+ channels in vascular myocytes through a Gαs‐induced stimulation of the cyclic AMP/protein kinase A pathway and the subsequent phosphorylation of the channels.

British Journal of Pharmacology (2000) 129, 1497–1505; doi:10.1038/sj.bjp.0703187
Rapid non‐genomic activation of cytosolic cyclic AMP‐dependent protein kinase activity and [Ca2+]i by 17β‐oestradiol in female rat distal colon
Authors: Doolan Christina M , Condliffe Steven B , Harvey Brian J 
Published: January 2005

In this study, the effect of 17β‐oestradiol on adenosine 3′ : 5′‐cyclic monophosphate (cyclic AMP)‐dependent protein kinase (PKA) activity was investigated.
Rapid (within 15 min) activation of basal PKA activity was observed in cytosolic fractions by 17β‐oestradiol but not by 17α‐oestradiol, progesterone or testosterone. This stimulation was abolished by the specific PKA inhibitor PKI but not by the classical oestrogen receptor antagonist tamoxifen.
17β‐Oestradiol did not stimulate basal PKA activity in membrane fractions or in cytosolic fractions from male rats.
The increase in cytosolic PKA activity was indirect as (i) it was inhibited by the adenylyl cyclase inhibitor SQ22536, (ii) it was mimicked by forskolin and (iii) 17β‐oestradiol did not cause a stimulation of basal PKA activity in either type I or type II commercially available PKA holoenzymes.
Protein kinase Cδ (PKCδ) was directly activated by 17β‐oestradiol. The specific PKC inhibitor, bisindolylmaleimide I (GF 109203X), abolished the 17β‐oestradiol‐induced PKA activation.
17β‐Oestradiol stimulated an increase in free intracellular calcium ion concentration ([Ca2+]i) in isolated female but not male rat colonic crypts. This was inhibited by verapamil, nifedipine and zero extracellular [Ca2+] but unaffected by tamoxifen. 17α‐Oestradiol, testosterone and progesterone failed to increase [Ca2+]i.
PKC and PKA inhibitors abolished the 17β‐oestradiol‐induced increase in [Ca2+]i.
These results demonstrate the existence of a novel 17β‐oestradiol‐specific PKA and Ca2+ signalling pathway, which is both sex steroid‐ and gender‐specific, in rat distal colonic epithelium.

British Journal of Pharmacology (2000) 129, 1375–1386; doi:10.1038/sj.bjp.0703193
Characterization of a novel nonpeptide vasopressin V2‐agonist, OPC‐51803, in cells transfected human vasopressin receptor subtypes
Authors: Nakamura Shigeki , Yamamura Yoshitaka , Itoh Shuji , Hirano Takahiro , Tsujimae Kenji , Aoyama Masashi , Kondo Kazumi , Ogawa Hidenori , Shinohara Tomoichi , Kan Keizo , Tanada Yoshihisa , Teramoto Shuji , Sumida Takumi , Nakayama Sunao , Sekiguchi Kazuo , Kambe Toshimi , Tsujimoto Gozoh , Mori Toyoki , Tominaga Michiaki 
Published: January 2005

We discovered the first nonpeptide arginine‐vasopressin (AVP) V2‐receptor agonist, OPC‐51803. Pharmacological properties of OPC‐51803 were elucidated using HeLa cells expressing human AVP receptor subtypes (V2, V1a and V1b) and compared with those of 1‐desamino‐8‐D‐arginine vasopressin (dDAVP), a peptide V2‐receptor agonist.
OPC‐51803 and dDAVP displaced [3H]‐AVP binding to human V2‐ and V1a‐receptors with Ki values of 91.9±10.8 nM (n=6) and 3.12±0.38 nM (n=6) for V2‐receptors, and 819±39 nM (n=6) and 41.5±9.9 nM (n=6) for V1a‐receptors, indicating that OPC‐51803 was about nine times more selective for V2‐receptors, similar to the selectivity of dDAVP. OPC‐51803 scarcely displaced [3H]‐AVP binding to human V1b‐receptors even at 10−4 M, while dDAVP showed potent affinity to human V1b‐receptors with the Ki value of 13.7±3.2 nM (n=4).
OPC‐51803 concentration‐dependently increased cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP) production in HeLa cells expressing human V2‐receptors with an EC50 value of 189±14 nM (n=6). The concentration‐response curve for cyclic AMP production induced by OPC‐51803 was shifted to the right in the presence of a V2‐antagonist, OPC‐31260.
At 10−5 M, OPC‐51803 did not increase the intracellular Ca2+ concentration ([Ca2+]i) in HeLa cells expressing human V1a‐receptors. On the other hand, dDAVP increased [Ca2+]i in HeLa cells expressing human V1a‐ and V1b‐receptors in a concentration‐dependent fashion.
From these results, OPC‐51803 has been confirmed to be the first nonpeptide agonist for human AVP V2‐receptors without agonistic activities for V1a‐ and V1b‐receptors. OPC‐51803 may be useful for the treatment of AVP‐deficient pathophysiological states and as a tool for AVP researches.

British Journal of Pharmacology (2000) 129, 1700–1706; doi:10.1038/sj.bjp.0703221
Blockade of the HERG human cardiac K+ channel by the antidepressant drug amitriptyline
Authors: Jo Su‐Hyun , Youm Jae Boum , Lee Chin O , Earm Yung E , Ho Won‐Kyung 
Published: January 2005

Amitriptyline has been known to induce QT prolongation and torsades de pointes which causes sudden death. We studied the effects of amitriptyline on the human ether‐a‐go‐go‐related gene (HERG) channel expressed in Xenopus oocytes and on the rapidly activating delayed rectifier K+ current (IKr) in rat atrial myocytes.
The amplitudes of steady‐state currents and tail currents of HERG were decreased by amitriptyline dose‐dependently. The decrease became more pronounced at more positive potential, suggesting that the block of HERG by amitriptyline is voltage dependent. IC50 for amitriptyline block of HERG current was progressively decreased according to depolarization: IC50 values at −30, −10, +10 and +30 mV were 23.0, 8.71, 5.96 and 4.66 μM, respectively.
Block of HERG by amitriptyline was use dependent: exhibiting a much faster block at higher activation frequency. Subsequent decrease in frequency after high activation frequency resulted in a partial relief of HERG blockade.
Steady‐state block by amitriptyline was obtained while depolarization to +20 mV for 0.5 s was applied at 0.5 Hz: IC50 was 3.26 μM in 2 mM [K+]o. It was increased to 4.78 μM in 4 mM [K+]o, suggesting that the affinity of amitriptyline on HERG was decreased by external K+.
In rat atrial myocytes bathed in 35°C, 5 μM amitriptyline blocked IKr by 55%. However, transient outward K+ current (Ito) was not significantly affected.
In summary, the data suggest that the block of HERG currents may contribute to arrhythmogenic side effects of amitriptyline.

British Journal of Pharmacology (2000) 129, 1474–1480; doi:10.1038/sj.bjp.0703222
Augmentation of SR Ca2+ release by rapamycin and FK506 causes K+‐channel activation and membrane hyperpolarization in bladder smooth muscle
Authors: Weidelt Th , Isenberg G 
Published: January 2005

The immunosuppressants rapamycin and FK506 are known to relax smooth muscle despite facilitating Ca2+ release through ryanodine‐receptors of the sarcoplasmic reticulum (SR). The apparent contradiction was studied in isolated guinea‐pig urinary bladder myocytes.
Modulation of spontaneous SR Ca2+ release was monitored by means of spontaneous transient outward currents (or STOCs) in isolated smooth muscle cells voltage‐clamped to −20 mV. Rapamycin (10 μM, n=18) significantly increased amplitude (50±12%, mean±s.d.), life time (77±19%), and time integral of STOCs (113±22%), and it reduced the interval between STOCs (20±7%). FK506 (20 μM, n=24) increased amplitude (15±7%), life time (50±7%), time integral (104±26%). Cyclosporin A (20 μM, n=18) had no significant effects on STOCs.
The basal cytoplasmic Ca2+ concentration ([Ca2+]c) measured by Indo1‐fluorescence was insensitive to rapamycin or FK506. Pretreatment with rapamycin (20 μM, 2 min) did not impair the SR Ca2+ load as can be concluded from caffeine‐induced Ca2+‐transients.
As it was expected from the enhanced STOC activity, the non‐clamped membrane was hyperpolarized by rapamycin (15±2 mV) or by FK506 (15±3 mV).
The data are consistent with the idea that rapamycin and FK506 augment spontaneous SR Ca2+ release by removal of FK‐binding proteins from the RyR‐complex. Smooth muscle relaxation is interpreted as negative Ca2+ feedback: augmented Ca2+ activation of STOCs induces membrane hyperpolarization that reduces Ca2+ influx through voltage gated channels.

British Journal of Pharmacology (2000) 129, 1293–1300; doi:10.1038/sj.bjp.0703223
Inhibition by various antipsychotic drugs of the G‐protein‐activated inwardly rectifying K+ (GIRK) channels expressed in Xenopus oocytes
Authors: Kobayashi Toru , Ikeda Kazutaka , Kumanishi Toshiro 
Published: January 2005

To investigate the effects of various chemical classes of antipsychotic drugs: haloperidol, thioridazine, pimozide and clozapine, on the G‐protein‐activated inwardly rectifying K+ (GIRK) channels, we carried out Xenopus oocyte functional assays with GIRK1 and GIRK2 mRNAs or GIRK1 and GIRK4 mRNAs.
In oocytes co‐injected with GIRK1 and GIRK2 mRNAs, application of each of the various antipsychotic drugs immediately caused a reduction of inward currents through the basally active GIRK channels. These responses were not observed in the presence of 3 mM Ba2+, which blocks the GIRK channels. In addition, in uninjected oocytes, none of the drugs tested produced any significant current response. These results indicate that all the antipsychotic drugs tested inhibited the brain‐type GIRK1/2 heteromultimeric channels. Furthermore, similar results were obtained in oocytes co‐injected with GIRK1 and GIRK4 mRNAs, indicating that the antipsychotic drugs also inhibited the cardiac‐type GIRK1/4 heteromultimeric channels.
All the drugs tested inhibited, in a concentration‐dependent manner, both types of GIRK channels with varying degrees of potency and effectiveness at micromolar concentrations. Only pimozide caused slight inhibition of these channels at nanomolar concentrations.
We conclude that the various antipsychotic drugs acted as inhibitors at the brain‐type and cardiac‐type GIRK channels. Our results suggest that inhibition of both types of GIRK channels by these drugs underlies some of the side effects, in particular seizures and sinus tachycardia, observed in clinical practice.

British Journal of Pharmacology (2000) 129, 1716–1722; doi:10.1038/sj.bjp.0703224
Pharmacological comparison of the effect of ibogaine and 18‐methoxycoronaridine on isolated smooth muscle from the rat and guinea‐pig
Authors: Mundey M K , Blaylock N A , Mason R , Glick S D , Maisonneuve I M , Wilson V G 
Published: January 2005

Ibogaine and 18‐methoxycoronaridine are naturally occurring alkaloids reported to possess antiaddictive properties in several models of drug dependence. We have examined their effect at μ‐opioid receptors regulating neurogenic contractions of several smooth muscle preparations and also against spontaneous contractions of the rat isolated portal vein.
Ibogaine (pIC50 5.28) and 18‐methoxycoronaridine (pIC50 5.05) caused a concentration‐dependent inhibition of cholinergic contractions of the guinea‐pig ileum which was not affected by the opioid receptor antagonist naloxone (1 μM).
In the rat isolated vas deferens ibogaine and 18‐methoxycoronaridine caused a concentration‐dependent enhancement of purinergic contractions. Both agents (30 μM) caused a 3–5 fold rightward displacement of DAMGO‐induced inhibition of purinergic contractions, but similar effects were observed for ibogaine against α2‐adrenoceptor‐mediated inhibition of neurogenic responses.
In the guinea‐pig isolated bladder both ibogaine (10 μM) and 18‐methoxycoronaridine (10 μM) caused a 2 fold increase in the purinergic component of neurogenic contractions without significantly altering cholinergic contractions or responses to exogenous ATP. In contrast, ibogaine (1–30 μM), but not 18‐methoxycoronaridine, caused a concentration‐dependent enhancement of spontaneous contractions of the rat isolated portal vein.
In summary, while ibogaine and 18‐methoxycoronaridine modulated electrically‐evoked contractions in the three preparations examined, we have no evidence for a selective interaction with pre‐junctional μ‐opioid receptors. The pronounced enhancement of purinergic contractions produced by both agents is a novel finding and worthy of further investigation.

British Journal of Pharmacology (2000) 129, 1561–1568; doi:10.1038/sj.bjp.0703227
Compounds that block both intermediate‐conductance (IKCa) and small‐conductance (SKCa) calcium‐activated potassium channels
Authors: Malik‐Hall M , Ganellin C R , Galanakis D , Jenkinson D H 
Published: January 2005

Nine bis‐quinolinyl and bis‐quinolinium compounds related to dequalinium, and previously shown to block apamin‐sensitive small conductance Ca2+‐activated K+ channels (SKCa), have been tested for their inhibitory effects on actions mediated by intermediate conductance Ca2+‐activated K+ channels (IKCa) in rabbit blood cells.
In most experiments, a K+‐sensitive electrode was employed to monitor the IKCa‐mediated net loss of cell K+ that followed the addition of the Ca2+ ionophore A23187 (2 μM) to red cells suspended at an haematocrit of 1% in a low K+ (0.12–0.17 mM) solution. The remainder used an optical method based on measuring the reduction in light transmission that occurred on applying A23187 (0.4 or 2 μM) to a very dilute suspension of red cells (haematocrit 0.02%).
Of the compounds tested, the most potent IKCa blocker was 1,12 bis[(2‐methylquinolin‐4‐yl)amino]dodecane (UCL 1407) which had an IC50 of 0.85±0.06 μM (mean±s.d.mean).
The inhibitory action of UCL 1407 and its three most active congeners was characterized by (i) a Hill slope greater than unity, (ii) sensitivity to an increase in external [K+], and (iii) a time course of onset that suggested use‐dependence. Also, the potency of the nonquaternary compounds tested increased with their predicted lipophilicity. These findings suggested that the IKCa blocking action resembles that of cetiedil rather than of clotrimazole.
Some quaternized members of the series were also active. The most potent was the monoquaternary UCL 1440 ((1‐[N‐[1‐(3,5‐dimethoxybenzyl)‐2‐methylquinolinium‐4‐yl]amino]‐10‐[N′‐(2‐methylquinolinium‐4yl)amino] decane (trifluoroacetate) which had an IC50 of 1.8±0.1 μM. The corresponding bisquaternary UCL 1438 (1,10‐bis[N‐[1‐(3,5‐dimethoxybenzyl)‐2‐methylquinolinium‐4‐yl]amino] decane bis(trifluoroacetate) was almost as active (IC50 2.7±0.3 μM).
A bis‐aminoquinolium cyclophane (UCL 1684) had little IKCa blocking action despite its great potency at SKCa channels (IC50 4.1±0.2 nM).
The main outcome is the identification of new intermediate‐conductance Ca2+‐activated K+ channel blockers with a wide range of IKCa/SKCa selectivities.

British Journal of Pharmacology (2000) 129, 1431–1438; doi:10.1038/sj.bjp.0703233