bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of endothelins and sarafotoxin 6c and L‐NAME on renal vasoconstriction in the anaesthetized rat
Authors: Marshall Joanne L , Johns Edward J 
Published: January 2005

An investigation was performed in pentobarbitone anaesthetized rats to compare the renal vasoconstrictor actions of endothelin‐1 (ET‐1), endothelin‐3 (ET‐3) and sarafotoxin 6c and their dependency on NO production.
Intra‐renal arterial infusion of ET‐1 and ET‐3, from 1–1000 ng had no effect on blood pressure, but reduced renal blood flow maximally by 82 and 81% with EC50 values of 510±18 and 1113±17 ng, respectively and correspondingly increased renal vascular resistance and decreased conductance.
Direct renal arterial administration of sarafotoxin 6c was without effect on blood pressure but caused a maximum reduction in renal blood flow of 56% at 300 ng and had an EC50 of 86±4 ng.
Administration of the selective ETA receptor antagonist FR139317 at 0.3 and 1.0 mg kg−1 had no effect on basal levels of blood pressure, renal vascular resistance or renal blood flow. The lower dose of FR139317 had no effect on the ET‐1 dose‐response curve for renal blood flow while at 1.0 mg kg−1, FR139317 reduced the EC50 to 363±32 ng (P<0.05).
Infusion of L‐NAME, 10 μg kg−1 min−1 increased blood pressure by approximately 15%, increased renal vascular resistance and decreased renal blood flow by some 40%. The EC50 values for renal blood flow were reduced to 358±68 ng (P<0.05) for ET‐1, 638±69 ng (P<0.05) for ET‐3 and 55±10 ng (P<0.01) for sarafotoxin 6c. The maximal reduction in renal blood flow induced by sarafotoxin 6c was raised (P<0.01) from 56% to approximately 100% and renal vascular resistance increased when NO production was blocked.
These results showed that the vasoconstrictor actions of ET‐1 and ET‐3 on resistance vessels controlling renal blood flow are mediated via ETB rather than ETA receptors. Moreover, both ET‐1 and ET‐3 dependent vasoconstrictions are slightly attenuated by concomitant NO production. By contrast, sarafotoxin 6c appears much more potent at the renal resistance vasculature and is much more powerfully modulated by NO.

British Journal of Pharmacology (1999) 128, 809–815; doi:10.1038/sj.bjp.0702846
Adrenocorticotropin reverses vascular dysfunction and protects against splanchnic artery occlusion shock
Authors: Squadrito Francesco , Guarini Salvatore , Altavilla Domenica , Squadrito Giovanni , Campo Giuseppe M , Arlotta Mariarita , Quartarone Cristina , Saitta Antonino , Cucinotta Domenico , Bazzani Carla , Cainazzo Maria M , Mioni Chiara , Bertolini Alfio , Caputi Achille P 
Published: January 2005

Tumour necrosis factor (TNF‐α) is involved in the pathogenesis of splanchnic artery occlusion (SAO) shock. On the other hand, inhibition of TNF‐α is an important component of the mechanism of action of melanocortins in reversing haemorrhagic shock. We therefore investigated the effects of the melanocortin peptide ACTH‐(1–24) (adrenocorticotropin fragment 1–24) on the vascular failure induced by SAO shock.
SAO‐shocked rats had a decreased survival rate (0% at 4 h of reperfusion, while sham‐shocked rats survived for more than 4 h), enhanced serum TNF‐α concentrations (755±81 U ml−1), decreased mean arterial blood pressure, leukopenia, and increased ileal leukocyte accumulation, as revealed by means of myeloperoxidase activity (MPO=9.4±1 U g−1 tissue). Moreover, aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE, 1 nM–10 μM) (Emax and ED50 in shocked rats=7.16 mN mg−1 tissue and 120 nM, respectively; Emax and ED50 in sham‐shocked rats=16.31 mN mg−1 tissue and 100 nM, respectively), reduced responsiveness to acetylcholine (ACh, 10 nM‐10 μM) (Emax and ED50 in shocked rats=30% relaxation and 520 nM, respectively; Emax and ED50 in sham‐shocked rats=82% relaxation and 510 nM, respectively) and increased staining for intercellular adhesion molecule‐1 (ICAM‐1).
ACTH‐(1–24) [160 μg kg−1 intravenously (i.v.), 5 min after SAO] increased survival rate [SAO+ACTH‐(1–24)=80% at 4 h of reperfusion], reversed hypotension, reduced serum TNF‐α (55±13 U ml−1), ameliorated leukopenia, reduced ileal MPO (1.2±0.2 U g−1 tissue), restored the reactivity to PE, improved the responsiveness to ACh and blunted the enhanced immunostaining for ICAM‐1 in the aorta.
Adrenalectomy only in part–but not significantly–reduced the ACTH‐induced shock reversal, the survival rate of SAO+ACTH‐(1–24) adrenalectomized rats being 60% at 4 h of reperfusion; and methylprednisolone (80 mg−1 i.v., 5 min after SAO) had a non‐significant effect (10% survival) at 4 h of reperfusion.
The present data show that melanocortins are effective also in SAO shock, their effect being, at least in part, mediated by reduced production of TNF‐α. Furthermore, they demonstrate, for the first time, that this inhibition is responsible for the adrenocorticotropin‐induced reversal of vascular failure and leukocyte accumulation.

British Journal of Pharmacology (1999) 128, 816–822; doi:10.1038/sj.bjp.0702848
Type I and II metabotropic glutamate receptor agonists and antagonists evoke cardiovascular effects after intrathecal administration in conscious rats
Authors: Li Xiao C , Beart Philip M , Monn James A , Jones Nicole M , Widdop Robert E 
Published: January 2005

In the present study, the role of metabotropic glutamate receptors (mGluRs) in central cardiovascular regulation in conscious rats was examined. To this end, agonists and antagonists for type I and II mGluRs were administered intrathecally, and the temporal changes in blood pressure and heart rate were recorded.
L‐glutamate (1 μmol) and the prototypical mGluR agonist (1S,3R)‐ACPD (0.1 and 0.3 μmol) both increased mean arterial pressure (MAP) and heart rate (HR), implicating functional mGluRs in the spinal cord. The type I mGluR agonist DHPG (0.01–0.1 μmol) evoked increases in MAP (max=25±5 mmHg) and HR (max=88±23 beats min−1). The duration of action, but not the maximum effects, were dose‐related and ranged from approximately 10 min to <90 min and 1 min to >90 min for MAP and HR, respectively.
The type I/II mGluR agonist CCG‐1 (0.1 and 0.3 μmol) caused smaller, variable increases in MAP and HR of intermediate duration (5–20 min), whereas the type II MGluR agonist APDC (0.1 and 1.0 μmol) caused marked, but transient (3–5 min), pressor and tachycardic responses. The highest doses of DHPG and CCG‐1, but not APDC, also evoked behavioural responses similar to a spontaneous nociceptive behavioural effect reported previously.
The type I and II mGluR antagonists (AIDA and LY307452, respectively) were also given approximately 5 min before the administration of the respective type I and II mGluR agonists (DHPG and APDC). Both compounds caused pressor and tachycardic responses, with the effect of AIDA, but not LY307452, returning to control levels before mGluR agonist administration. AIDA significantly attenuated the overall cardiovascular effects of DHPG, while LY307452 significantly attenuated the overall cardiovascular effects of APDC.
These results indicate that functional type I and II mGluRs exist in the spinal cord, and that their activation evokes prolonged cardiovascular effects.

British Journal of Pharmacology (1999) 128, 823–829; doi:10.1038/sj.bjp.0702850
Novel antimigraineur dotarizine releases Ca2+ from caffeine‐sensitive Ca2+ stores of chromaffin cells
Authors: Novalbos Jesús , Abad‐Santos Francisco , Zapater Pedro , Alvarez Javier , Alonso María Teresa , Montero Mayte , García Antonio G 
Published: January 2005

The novel antimigraineur, dotarizine (30 μM), increased cytosolic Ca2+ concentration, [Ca2+]c, in fura‐2‐loaded bovine adrenal chromaffin cells. This increase was transient, reached a peak in about 2–5 min (0.53±0.07 μM; n=19) and then declined to basal levels over a further 5 min period.
This transient rise of [Ca2+]c was mimicked by 1 μM thapsigargin and by 30 μM cyclopiazonic acid (CPA), but not by 30 μM flunarizine. Both thapsigargin and CPA occluded the effects of dotarizine and vice versa.
All three compounds suppressed the transient [Ca2+]c rises induced by caffeine (10 mM, 10 s); blockade induced by thapsigargin was irreversible and that induced by CPA and dotarizine was reversible.
Of the three compounds, only dotarizine blocked reversibly the [Ca2+]c spikes induced by short pulses of high K+ (70 mM, 5 s), suggesting that dotarizine blocks voltage‐dependent Ca2+ channels but CPA and thapsigargin do not.
Dotarizine caused a gradual and reversible depletion of endoplasmic reticulum (ER) Ca2+ in chromaffin cells transfected with ER‐targeted aequorin. CPA had a similar effect.
These data show that dotarizine shares with thapsigargin and CPA the ability to deplete Ca2+ in the ER; this novel action of dotarizine could be relevant to its prophylactic effects in migraine. Unlike thapsigargin and CPA, however, dotarizine additionally and reversibly blocks Ca2+ entry through voltage‐dependent Ca2+ channels.

British Journal of Pharmacology (1999) 128, 621–626; doi:10.1038/sj.bjp.0702853
Novel strategies for the design of receptor‐selective vasopressin analogues: Aib‐substitution and retro‐inverso transformation
Authors: Howl John , Prochazka Zdenko , Wheatley Mark , Slaninová Jirina 
Published: January 2005

We determined the pharmacological profile of novel backbone‐modified peptides designed as protease‐resistant, selective analogues of AVP. Binding affinities of peptides were determined at both V1A and V2 subtypes of vasopressin receptor (VPR). Biological potencies of selected peptides were tested in pressor and antidiuretic bioassays.
Substitution of the achiral α‐aminoisobutyric acid (Aib) at position 4 or 7 of AVP produced peptides that selectively bound the V2 VPR. Both [Aib4]AVP (140 IU mg−1) and [Aib7]AVP (36 IU mg−1) are selective antidiuretic agonists with little or no activity in uterotonic and pressor assays.
[Aib4] and [Aib7] derivatives of the linear V1A‐selective antagonist [PhaaDTyr(Et)2Arg6Tyr(NH2)9]AVP bound selectively and with high affinity (Kd 0.51 and 4.1 nM respectively) to the V1A VPR. Bioassays confirmed that these peptides were potent antivasopressor agents (pA2 8.10 and 8.36 respectively).
A total retro‐inverso strategy was used to prepare protease‐resistant mimetics of both AVP and linear V1A‐selective antagonists. Cyclic retro‐inverso mimetics of AVP did not bind either V1A or V2 VPRs. In contrast, rationally designed retro‐inverso mimetics of linear V1A‐selective antagonists selectively bound the V1A VPR.
Our findings indicate novel methods to improve the pharmacodynamic and pharmacokinetic parameters of neurohypophysial hormone analogues which could be equally applicable to other peptide‐receptor systems.

British Journal of Pharmacology (1999) 128, 647–652; doi:10.1038/sj.bjp.0702857
Acetylcholine‐induced relaxation of peripheral arteries isolated from mice lacking endothelial nitric oxide synthase
Authors: Waldron G J , Ding H , Lovren F , Kubes P , Triggle C R 
Published: January 2005

Acetycholine‐mediated relaxations in phenylephrine‐contracted aortas, femoral and mesenteric resistance arteries were studied in vessels from endothelial nitric oxide synthase knock‐out (eNOS −/−) and the corresponding wild‐type strain (eNOS +/+) C57BL6/SV19 mice.
Aortas from eNOS (+/+) mice relaxed to acetylcholine in an endothelium‐dependent NG‐nitro‐L‐arginine (L‐NOARG) sensitive manner. Aortas from eNOS (−/−) mice did not relax to acetylcholine but demonstrated enhanced sensitivity to both authentic NO and sodium nitroprusside.
Relaxation to acetylcholine in femoral arteries was partially inhibited by L‐NOARG in vessels from eNOS (+/+) mice, but relaxation in eNOS (−/−) mice was insensitive to a combination of L‐NOARG and indomethacin and the guanylyl cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ). The L‐NOARG/ODQ/indomethacin‐insensitive relaxation to acetylcholine in femoral arteries was inhibited in the presence of elevated (30 mM) extracellular KCl.
In mesenteric resistance vessels from eNOS (+/+) mice, the acetylcholine‐mediated relaxation response was completely inhibited by a combination of indomethacin and L‐NOARG or by 30 mM KCl alone. In contrast, in mesenteric arteries from eNOS (−/−) mice, the acetylcholine‐relaxation response was insensitive to a combination of L‐NOARG and indomethacin, but was inhibited in the presence of 30 mM KCl.
These data indicate arteries from eNOS (−/−) mice demonstrate a supersensitivity to exogenous NO, and that acetylcholine‐induced vasorelaxation of femoral and mesenteric vessels from eNOS (−/−) mice is mediated by an endothelium‐derived factor that has properties of an EDHF but is neither NO nor prostacyclin. Furthermore, in mesenteric vessels, there is an upregulation of the role of EDHF in the absence of NO.

British Journal of Pharmacology (1999) 128, 653–658; doi:10.1038/sj.bjp.0702858
Deficiency in myocardial NO biosignalling after cardioplegic arrest: mechanisms and contribution to post‐storage mechanical dysfunction
Authors: Rach Craig , Gandhi Manoj , Docherty John , Finegan Barry A , Clanachan Alexander S 
Published: January 2005

In order to understand mechanisms that limit the safe ischaemic time of donor hearts, this study evaluated NO/cyclic GMP biosignalling in the recovery of function after cardioplegia and hypothermic storage.
Hearts removed from anaesthetized rats were either perfused in working mode (Fresh) or arrested (St. Thomas' II cardioplegia) and stored at 3°C for 8 h (CPL) prior to working mode perfusion. LV work and indices of the production of NO (Ca2+‐dependent and Ca2+‐independent NOS), cyclic GMP (soluble guanylyl cyclase (sGC) and GTP) and superoxide (xanthine oxidase (XO) and xanthine dehydrogenase (XDH)) were measured.
Relative to Fresh hearts, CPL hearts were deficient in cyclic GMP and had poor function. Correction of cyclic GMP deficiency (SNP, 200 μM) improved LV work and LV compliance. SNP effects were prevented by inhibition of sGC (ODQ, 3 μM), and potentiated by inhibition of cyclic GMP‐dependent phosphodiesterase (zaprinast, 20 μM). SNP (200 μM) had no effect on function of Fresh hearts.
NOS activities (pH=7.2) were similar in CPL and Fresh hearts, but at end‐ischaemic pH (6.3), Ca2+‐dependent NOS activity was reduced. The sensitivity of sGC to SNP was greater, and activities of XO and XDH were higher, in CPL than in Fresh hearts.
The deficiency in NO biosignalling in CPL hearts may arise due to acidosis‐induced inhibition of NOS activity, reduced availability of GTP and/or enhanced inactivation of NO by superoxide. These findings provide rationales for novel strategies to prevent the deficiency in NO biosignalling and so improve the function of the transplanted heart.

British Journal of Pharmacology (1999) 128, 891–902; doi:10.1038/sj.bjp.0702863
Nicotinic acetylcholine receptor blocking effect of guanethidine in the rat gastric fundus
Authors: Blommaart P J E , Ferwerda G , Kodde A , Tytgat G N J , Boeckxstaens G E 
Published: January 2005

Guanethidine is commonly used as a drug to investigate adrenergic neurotransmission and, in combination with atropine, to realize non‐adrenergic non‐cholinergic (NANC) conditions. Previous studies suggested a nicotinic acetylcholine receptor blocking effect of guanethidine. Therefore, we investigated the effect of increasing concentrations of guanethidine (0.1–100 μM) on nicotine‐induced relaxations of longitudinal muscle strips of rat gastric fundus.
In the presence of 1 μM atropine and 3 μM guanethidine, nicotine (30 μM) induces a fast and sustained relaxation which is partly inhibited by the nitric oxide synthase inhibitors Nω‐nitro‐L‐arginine (L‐NOARG) and Nω‐nitro‐L‐arginine methyl ester (L‐NAME) (both 30 and 100 μM). One μM tetrodotoxin (TTX) completely blocks this nicotine‐induced relaxation.
High concentrations of guanethidine (10 μM), but not adrenoceptor blockade by the α‐adrenoceptor antagonist phentolamine in combination with the β‐adrenoceptor antagonist nadolol (both 3 μM), inhibit the nicotine‐induced relaxation.
Guanethidine (0.1–100 μM) has no effect on relaxations induced by electrical field stimulation (EFS; 1–8 Hz), nitric oxide (NO; 0.01–1 μM), vasoactive intestinal polypeptide (VIP; 0.1–10 nM) or isoprenaline (1–10 nM).
We conclude that high concentrations of guanethidine (10 μM) block nicotine‐induced NANC relaxations of longitudinal muscle strips of the rat gastric fundus most likely at the level of the nicotinic acetylcholine receptor.

British Journal of Pharmacology (1999) 128, 903–908; doi:10.1038/sj.bjp.0702865
Distribution and regulation of cyclooxygenase‐2 in carrageenan‐induced inflammation
Authors: Nantel François , Denis Danielle , Gordon Robert , Northey Angela , Cirino Maria , Metters Kathleen M , Chan Chi Chung 
Published: January 2005

We characterized the regulation of cyclooxygenase‐2 (COX‐2) at the mRNA, protein and mediator level in two rat models of acute inflammation, carrageenan‐induced paw ædema and mechanical hyperalgesia.
Carrageenan was injected in the hind paw of rat at low (paw ædema) and high doses (hyperalgesia). COX‐2 and prostaglandin E2 (PGE2) levels were measured by RT–PCR and immunological assays. We also determined the distribution of COX‐2 by immunohistochemistry.
The injection of carrageenan produced a significant and parallel induction of both COX‐2 and PGE2. This induction was significantly higher in hyperalgesia than in paw ædema. This was probably due to the 9 fold higher concentration of carrageenan used to provoke hyperalgesia.
Immunohistochemical examination showed COX‐2 immunoreactivity in the epidermis, skeletal muscle and inflammatory cells of rats experiencing hyperalgesia. In paw ædema however, only the epidermis showed positive COX‐2 immunoreactivity.
Pretreatment with indomethacin completely abolished the induction of COX‐2 in paw ædema but not in hyperalgesia.
These results suggest that multiple mechanisms regulate COX‐2 induction especially in the more severe model. In carrageenan‐induced paw ædema, prostanoid production have been linked through the expression of the COX‐2 gene which suggest the presence of a positive feedback loop mechanism.

British Journal of Pharmacology (1999) 128, 853–859; doi:10.1038/sj.bjp.0702866
The role of protease‐activated receptor‐2 (PAR2) in the modulation of beating of the mouse isolated ureter: lack of involvement of mast cells or sensory nerves
Authors: Moffatt J D , Cocks T M 
Published: January 2005

The localization of protease‐activated receptor‐2 (PAR2) and the effects of PAR2 activators were investigated in the mouse isolated ureter in order to test the hypothesis that PAR2 activation may initiate neuropeptide release from sensory nerve fibres and hence contribute to inflammation.
PAR2 was localized by fluorescence immunohistochemistry to both the smooth muscle and epithelium of the ureter. Macrophage‐like cells in the adventitia of the ureter were also PAR2‐immunoreactive. PAR2‐immunoreactivity was not observed in mast cells or nerve fibres.
In circular muscle preparations of the ureter in which continuous rhythmic beating was induced by KCl (20 mM) and the thromboxane A2 mimetic U46619 (0.3 μM), trypsin (0.3 U ml−1) reduced beat frequency to 84.6±2.0% of control rates. The PAR2‐selective peptide agonist SLIGRL‐NH2 concentration‐dependently (0.1–3.0 μM) slowed beat frequency to a maximum of 72.7±2.0%.
Histamine (1–300 μM) was more efficacious than SLIGRL‐NH2 in inhibiting ureter beat frequency in a concentration‐dependent manner to a maximum (at 300 μM) of 7.9±2.5% of the control rate.
Pretreatment of preparations with capsaicin (10 μM for 30 min) markedly attenuated the inhibitory effect of histamine, but not that of SLIGRL‐NH2, indicating a role for sensory nerves in the inhibitory effect of histamine only.
The inhibitory effect of SLIGRL‐NH2 on ureter beat frequency was unaffected by the nitric oxide (NO) synthase inhibitor, L‐NOARG (100 μM) or the cyclo‐oxygenase inhibitor, indomethacin (3 μM).
In conclusion, PAR2 activation causes inhibition of beating in the mouse ureter that is not mediated by axon reflex release of inhibitory neuropeptides. This inhibitory effect of PAR2 appears to be mediated directly on smooth muscle cells, although the contribution of non‐NO, non‐prostanoid epithelium‐derived factors cannot be ruled out.

British Journal of Pharmacology (1999) 128, 860–864; doi:10.1038/sj.bjp.0702871
Autoregulation of nitric oxide‐soluble guanylate cyclase‐cyclic GMP signalling in mouse thoracic aorta
Authors: Hussain Monira B , Hobbs Adrian J , MacAllister Raymond J 
Published: January 2005

The sensitivity of the soluble guanylate cyclase (sGC)‐cyclic guanosine‐3′,5′‐monophosphate (cyclic GMP) system to nitric oxide (NO) was investigated in mouse aorta from wild type (WT) and NO synthase (NOS) knockout (KO) animals.
The NO donor, spermine‐NONOate (SPER‐NO) was more potent in aortas from eNOS KO mice compared to WT (pEC50 7.30±0.06 and 6.56±0.04, respectively; n=6; P<0.05). In contrast, the non‐NO based sGC activator, YC‐1 was equipotent in vessels from eNOS WT and KO mice. The sensitivity of aortas from nNOS and iNOS KO animals to SPER‐NO was unchanged. Forskolin (an adenylate cyclase activator), was equipotent in vessels from eNOS WT and KO animals.
The cyclic GMP analogue, 8‐Br‐cGMP was equipotent in eNOS WT and KO mice (pEC50 4.38±0.04 and 4.40±0.05, respectively; n=5; P>0.05). Zaprinast (10−5 M) a phosphodiesterase type V (PDE V) inhibitor, had no effect on the response to SPER‐NO in vessels from eNOS WT or KO mice.
The NOS inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME; 3×10−4 M) increased the potency of SPER‐NO in aortas from WT mice (pEC50 6.64±0.02 and 7.37±0.02 in the absence and presence of L‐NAME, respectively; n=4; P<0.05).
In summary, there is increased sensitivity of vessels from eNOS KO animals to NO. Cyclic AMP‐mediated dilatation is unchanged, consistent with a specific up‐regulation of sGC–cyclic GMP signalling. The functional activity of cyclic GMP‐dependent protein kinase (G‐kinase) and PDE V was also unchanged, suggesting that sGC is the site of up‐regulation. These alterations in the sensitivity of the sGC–cyclic GMP pathway might represent a mechanism for the dynamic regulation of NO bioactivity.

British Journal of Pharmacology (1999) 128, 1082–1088; doi:10.1038/sj.bjp.0702874
Investigation of the prejunctional α2‐adrenoceptor mediated actions of MDMA in rat atrium and vas deferens
Authors: Lavelle Aisling , Honner Valerie , Docherty J R 
Published: January 2005

We have investigated the effects of methylenedioxymethamphetamine (MDMA, ‘ecstasy’) on peripheral noradrenergic neurotransmission in the rat.
In rat atrial slices pre‐incubated with [3H]‐noradrenaline and in the presence of desipramine (1 μM) to prevent effects of MDMA on basal outflow of tritium, MDMA (10 μM) significantly inhibited the release of tritium evoked by short trains of six pulses at 100 Hz every 10 s for 3 min. This effect did not occur in the presence of the α2‐adrenoceptor antagonist yohimbine (1 μM).
In epididymal portions of rat vas deferens in the presence of nifedipine (10 μM), MDMA produced a concentration‐dependent inhibition of single pulse nerve stimulation‐evoked contractions with a pD2 of 5.88±0.16 (n=4). Inhibitory effects of MDMA were antagonized by the α2‐adrenoceptor antagonist yohimbine (0.3 μM), but not by the 5‐hydroxytryptamine receptor antagonist cyanopindolol in a concentration (1 μM) which markedly antagonized the inhibitory actions of the 5‐HT‐1 receptor agonist 5‐carboxamidotryptamine.
In prostatic portions of rat vas deferens in the presence of cocaine (3 μM), MDMA produced a concentration‐dependent inhibition of single pulse nerve stimulation‐evoked contractions with a pD2 of 5.12±0.21 (n=4). In the absence of cocaine, only the highest concentration of MDMA (30 μM) produced an inhibition, but the α2‐adrenoceptor antagonist yohimbine (0.3 μM) converted the response to MDMA from inhibition to potentiation of the stimulation‐evoked contraction.
In radioligand binding studies, MDMA showed similar affinities for α2B, α2C and α2D‐adrenoceptor sites, with pKi values of 5.14±0.16, 5.11±0.05 and 5.31±0.14, respectively.
It is concluded that MDMA has significant α2‐adrenoceptor agonist actions.

British Journal of Pharmacology (1999) 128, 975–980; doi:10.1038/sj.bjp.0702875