bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monoaminergic involvement in the pharmacological actions of buspirone
Authors: Skolnick Phil , Weissman Ben Avi , Youdim Moussa B.H. 
Published: July 2012

Buspirone, MJ‐13805 and MJ‐13653 did not produce a ‘5‐hydroxytryptamine (5‐HT) syndrome’ in rats at doses up to 20 mg kg−1.
These drugs were very weak 5‐HT uptake blockers (IC50 ≫ 10 μM) compared to drugs such as chlorimipramine.
These drugs did not inhibit either monoamine oxidase (MAO)‐A or MAO‐B.
The Ki values for these agents as inhibitors of [3H]‐5‐HT and [3H]‐ketanserin binding to rat frontal cortex or hippocampal membranes were in the μM range, well above the brain concentrations achieved after an oral dose of 25 mg kg−1.
Parenterally administered buspirone blocked apomorphine‐induced sterotypy, inhibited the 5‐HT syndrome elicited by 5‐methoxy‐N,N‐dimethyltryptamine, and delayed the onset of p‐chloroamphetamine induced behaviours.
Effects of glutamic acid analogues on identifiable giant neurones, sensitive to β‐hydroxy‐L‐glutamic acid, of an African giant snail (Achatina fulica Férussac)
Authors: Nakajima Tadashi , Nomoto Kyosuke , Ohfune Yasufumi , Shiratori Yoshimune , Takemoto Tsunematsu , Takeuchi Hiroshi , Watanabe Kazuko 
Published: July 2012

The effects of the seven glutamic acid analogues, α‐kainic acid, α‐allo‐kainic acid, domoic acid, erythro‐L‐tricholomic acid, DL‐ibotenic acid, L‐quisqualic acid and allo‐γ‐hydroxy‐L‐glutamic acid were examined on six identifiable giant neurones of an African giant snail (Achatina fulica Férussac).
The neurones studied were: PON (periodically oscillating neurone), d‐RPLN (dorsal‐right parietal large neurone), VIN (visceral intermittently firing neurone), RAPN (right anterior pallial neurone), FAN (frequently autoactive neurone) and v‐RCDN (ventral‐right cerebral distinct neurone). Of these, d‐RPLN and RAPN were excited by the two isomers (erythro‐ and threo‐) of β‐hydroxy‐L‐glutamic acid (L‐BHGA), whereas PON, VIN, FAN and v‐RCDN were inhibited. L‐Glutamic acid (L‐Glu) had virtually no effect on these neurones.
α‐Kainic acid and domoic acid showed marked excitatory effects, similar to those of L‐BHGA, on d‐RPLN and RAPN. Their effective potency quotients (EPQs), relative to the more effective isomer of L‐BHGA were: 0.3 for both substances on d‐RPLN, and 1 for α‐kainic acid and 3‐1 for domoic acid on RAPN. α‐Kainic acid also had excitatory effects on FAN and v‐RCDN (EPQ for both: 0.3), which were inhibited by L‐BHGA but excited by γ‐aminobutyric acid (GABA).
Erythro‐L‐tricholomic acid showed marked effects, similar to those of L‐BHGA, on VIN (EPQ: 0.3) and RAPN (EPQ: 3‐1), but produced weaker effects on PON and d‐RPLN (EPQ: 0.1).
DL‐Ibotenic acid produced marked effects, similar to those of L‐BHGA, on PON, VIN (EPQ for both: 1) and RAPN (EPQ: 1‐0.3), but had weak effects on d‐RPLN (EPQ: <0.1) and FAN (EPQ: 0.1). It had excitatory effects on v‐RCDN (EPQ: 0.1). This neurone was inhibited by L‐BHGA but excited by GABA.
L‐Quisqualic acid showed the same effects as L‐BHGA on all of the neurones examined (EPQ range 30–0.1). It was the most potent of the compounds tested on RAPN (EPQ: 30‐10), FAN (EPQ:30) and v‐RCDN (EPQ:3).
α‐Allo‐kainic acid and allo‐γ‐hydroxy‐L‐glutamic acid had no obvious effect on any of the neurones examined.
As described above, the responses of the neurones examined to these substances varied widely. However, L‐quisqualic acid generally had effects on the neurones similar to those of L‐BHGA; the L‐BHGA‐excited neurones were also excited by α‐kainic acid and domoic acid.
The effects of triazolobenzodiazepines in two animal tests of anxiety and in the holeboard
Authors: File Sandra E. , Pellow Sharon 
Published: July 2012

In addition to possessing anti‐anxiety activity in man, triazolobenzodiazepines have been reported to have antidepressant and antipanic properties. In this they differ from classical 1,4‐benzodiazepines that have only anti‐anxiety activity. The purpose of the present study was to examine the effects of the triazolobenzodiazepines in two animal tests of anxiety and in the holeboard, to see whether clear differences could be observed between them and the 1,4‐benzodiazepines.
After acute administration, U‐43,465 (16 mg kg−1) had a significant anxiolytic effect in the social interaction test. Neither adinazolam (1–3.5 mg kg−1) nor alprazolam (0.125‐2 mg kg−1) had a significant effect. It is suggested that this is because, with adinazolam and alprazolam, doses at which anxiolytic effects can be observed are close to those at which sedative effects can be observed.
U‐43,465 (8–16 mg kg−1) and alprazolam (1–2 mg kg−1) had significant anxiolytic effects in the elevated plus‐maze test of anxiety.
U‐43,465 (8–32 mg kg−1), adinazolam (0.5‐5 mg kg−1) and alprazolam (0.2‐2.0 mg kg−1) caused dose‐related reductions in exploratory head‐dipping, locomotor activity and rearing in the holeboard.
In general the results seen in the three tests with the triazolobenzodiazepines alprazolam and adinazolam were similar to those seen with classical 1,4‐benzodiazepines. With U‐43,465, however, an anxiolytic effect was observed in the social interaction test after acute treatment; chronic treatment is required to see an effect with classical 1,4‐benzodiazepines. In this U‐43,465 resembles the effects of several novel non‐benzodiazepine putative anxiolytic compounds that are believed to have less sedative potential than the benzodiazepines.
The effect of chronic haloperidol treatment on some cardiovascular parameters in cats
Authors: Bentley G.A. , Copeland I.W. 
Published: July 2012

Blood pressure, heart rate and evoked cardiovascular reflexes were examined in cats following chronic treatment with haloperidol, at a dose of 1 mg kg−1 per day, orally for 23 days. Five days after the final dose the animals were anaesthetized and tested for their reaction to various cardiovascular stimuli and to a number of agonist and antagonist drugs, given both intravenously and into the vertebral artery.
It was found that treatment with haloperidol caused hypertension in the cats, as well as a potentiation of the pressor response to bilateral carotid occlusion. The response to 30° head‐up tilting was also altered so that in treated cats, the blood pressure returned to normal more rapidly during the tilt.
There was no difference in the heart rate of the two groups of cats, nor in the pressor response to intravenous noradrenaline or angiotensin II or to afferent brachial nerve stimulation, nor was the depressor action of bradykinin altered. Hexamethonium reduced the blood pressure in both control and treated cats to approximately the same level. Blood O2, CO2, pH and bicarbonate levels were also unaltered by the treatment, as was plasma renin activity.
Of the drugs given into the vertebral artery, only noradrenaline, prazosin, ketanserin and haloperidol caused a significantly greater fall in blood pressure in treated than in control cats, while clonidine and St91 were equally effective in both groups. These results suggest that haloperidol treatment has caused a greater modulation of central α1‐ than of α2‐adrenoceptors.
Effect of the endogenous analgesic dipeptide, kyotorphin, on transmitter release in sympathetic ganglia
Authors: Hirai K. , Katayama Y. 
Published: July 2012

The effects of kyotorphin and the synthetic analogue, D‐kyotorphin, on cholinergic fast excitatory postsynaptic potentials (fast‐e.p.s.ps) were studied using intracellular recordings from bullfrog sympathetic ganglion cells.
Kyotorphin and D‐kyotorphin (1–100 μM) increased the amplitude and the mean quantal content of the fast‐e.p.s.p. without changing the mean quantal size in a low Ca2+/high Mg2+ medium.
Kyotorphin and D‐kyotorphin (1–100 μM) did not change the resting membrane potential, input membrane resistance, the amplitude and duration of action potentials and the sensitivity to the transmitter, acetylcholine (ACh), of the ganglion cells.
The facilitatory effect of D‐kyotorphin on the fast‐e.p.s.p. was reversibly inhibited by naloxone (10 μM).
These results indicate that kyotorphin may increase transmitter release from preganglionic nerve terminals. The possible mechanisms underlying this action of kyotorphin are discussed.
Application of the operational model of agonism to establish conditions when functional antagonism may be used to estimate agonist dissociation constants
Authors: Leff P. , Martin G.R. , Morse J.M. 
Published: July 2012

The operational model of agonism (Black & Leff, 1983) has been used to analyse comparatively functional antagonism and irreversible antagonism as methods for estimating agonist dissociation constants (KAs).
A general condition is established in terms of the model parameters which defines the type of experimental interventions at the receptor and the post‐receptor level that allow valid KA estimation.
It is shown that functional antagonism and other post‐receptor interventions may produce changes in agonist‐concentration effect curves which are qualitatively indistinguishable but quantitatively distinct, from those produced by irreversible antagonism.
Experimental data obtained with the guinea‐pig tracheal strip preparation are in keeping with the theoretical predictions and show how studies using functional antagonism may overestimate agonist affinity.
In general, functional antagonism, unlike irreversible antagonism, is in principle an unreliable method for quantifying agonism.
Inhibition of monoamine oxidase in 5‐ hydroxytryptaminergic neurones by substituted p‐aminophenylalkylamines
Authors: Ask Anna‐Lena , Fagervall Ingrid , Florvall L. , Ross S.B. , Ytterborn Susanne 
Published: July 2012

A series of substituted p‐aminophenethylamines and some related compounds were examined with regards to the inhibition of monoamine oxidase (MAO) in vivo inside and outside 5‐hydroxytryptaminergic neurones in the rat hypothalamus. This was recorded as the protection against the irreversible inhibition of MAO produced by phenelzine by determining the remaining deaminating activity in the absence and presence of citalopram using a low (0.1 μM) concentration of [14C]‐5‐hydroxytryptamine (5‐HT) as substrate.
Some of the phenethylamines were much more potent inside than outside the 5‐hydroxytryptaminergic neurones. This neuronal selectivity was antagonized by pretreatment of the rats with norzimeldine, a 5‐HT uptake inhibitor, which indicates that these compounds are accumulated in the 5‐HT nerve terminals by the 5‐HT pump.
Selectivity was obtained for compounds with dimethyl, monomethyl or unsubstituted p‐amino groups. An isopropyl group appears to substitute for the dimethylamino group but with considerably lower potency. Compounds with 2‐substitution showed selectivity for aminergic neurones and this effect decreased with increased size of the substituent. The 2,6‐dichloro derivative FLA 365 had, however, no neuronal selective action but was a potent MAO inhibitor. Substitutions in the 3‐ and 5‐ positions decreased both potency and selectivity.
Prolongation of the side chain with one methylene group abolished the preference for the MAO in 5‐hydroxytryptaminergic neurones although the MAO inhibitory potency remained. The selectivity disappeared by increasing the α‐substituent to an ethyl group but remained for the α,α‐dimethyl substituted derivatives.
It is concluded that compounds which are (1) transported by the 5‐HT pump and (2) potent reversible MAO‐A inhibitors produce pronounced inhibition of MAO in 5‐hydroxytryptaminergic neurones.
Central δ‐opioid receptor interactions and the inhibition of reflex urinary bladder contractions in the rat
Authors: Dray A. , Nunan L. , Wire W. 
Published: July 2012

The in vivo effects of a number of opioid agonists and antagonists were studied on the spontaneous reflex contractions of the urinary bladder recorded isometrically in the rat anesthetized with urethane. All substances were administered into the central nervous system by the intracereboventricular (i.c.v.) or spinal intrathecal (i.t.) route.
The conformationally restricted enkephalin analogues [2‐D‐penicillamine, 5‐L‐cysteine] enkephalin (DPLCE), [2‐D‐penicillamine, 5‐L‐penicillamine] enkephalin (DPLPE) and [2‐D‐penicillamine, 5‐D‐penicillamine] enkephalin (DPDPE) produced dose‐related inhibition of reflex bladder contractions when administered by the i.c.v. or i.t. route.
Both the novel δ‐opioid receptor antagonist ICI 154,129 (200–600 μg) [N,N‐bisallyl‐Tyr‐Gly‐Gly‐ψ‐(CH2S)‐Phe‐Leu‐OH) and ICI 174,864 (1–3 μg) [N,N‐diallyl‐Tyr‐Aib‐Aib‐Phe‐Leu‐OH: Aib = α‐aminoisobutyric acid] attenuated or abolished the effects of DPLCE, DPLPE and DPDPE when administered by the i.c.v. or i.t. route. The antagonism observed was selective since the equipotent inhibition produced by the μ‐opioid receptor agonist [D‐Ala2, Me‐Phe4, Gly(ol)5] enkephalin (DAGO) was unaffected. Overall, ICI 154,129 was considerably weaker than ICI 174,864 and both antagonists inhibited bladder activity at doses higher than those required to demonstrate δ‐receptor antagonism.
Further studies of the agonistic effect of ICI 174,864 showed that it was insensitive to low doses of naloxone (2 μg, i.c.v. or i.t.) but could be abolished by higher (10–15 μg) doses of naloxone. These observations suggested that the agonistic effect of ICI 174,864 was not mediated by μ‐opioid receptor.
β‐Endorphin (0.2‐1.0 μg, i.c.v.) inhibited bladder contractions but following recovery from this effect, appeared to prevent the expression of δ‐receptor antagonism by ICI 174,864. In addition a previously subthreshold dose of ICI 174,864 now exhibited marked agonistic activity. The inhibitory effect of a submaximal dose of DPDPE was also potentiated by β‐endorphin under these circumstances.
These observations suggest that supra‐spinal and spinal δ‐opioid receptors are involved in the opioid‐mediated inhibition of reflex bladder contractions in the rat. Moreover β‐endorphin may be important in regulating central δ‐opioid receptors.
Affinity and efficacy correlate with chemical structure more than potency does in a series of pentatomic cyclic muscarinic agonists
Authors: Angeli P. , Brasili L. , Giannella M. , Gualtieri F. , Pigini M. 
Published: July 2012

The efficacy and affinity of nine pentatomic cyclic muscarinic agonists were determined on the guinea‐pig ileum, according to the method of Furchgott & Bursztyn (1967).
The efficacy and affinity of these agonists are affected differently by structural modifications.
Our results suggest that a strong dipole oriented in the same direction as that of the hydroxy group of muscarine, or the presence of a polarizable atom in the same position, are important for efficacy.
Contractor responses of the isolated colon of the mouse to morphine and some opioid peptides
Authors: Fontaine Jeanine , Reuse Jean 
Published: July 2012

Morphine (1 times 10−8‐1 times 10−4M), fentanyl (1 times 10−9− 1 times 10−5M) and alfentanyl (1 times 10−10 − 1 times 10−5M) as well as methionine enkephalin [Met5]enkephalin (1 times 10−11 − 1 times 10−8M), [D‐Ala2, Met5]enkephalin (1 times 10−12 − 1 times 10−8M) and dynorphin A(1 − 13) (1 times 10−9 − 1 times 10−6M) caused a contractor response of the longitudinal musculature of the terminal colon of the mouse.
These effects were competitively antagonized by naloxone. The pA2 values obtained for naloxone antagonism of morphine and opioid peptides and the high sensitivity of the preparation to enkephalins suggest the presence of δ‐opiate receptors in this preparation but μ‐and κ‐receptors may also be present.
Opiate‐induced contractions in the mouse colon were abolished by tetrodotoxin and after incubation with indomethacin.
It is concluded that the excitatory actions of the opiates in the mouse colon are mediated via opiate receptors located on nerves which do not release acetylcholine, noradrenaline or 5‐hydroxytryptamine. The opiates may produce their action by removing an inhibitory neural influence (the nature of which remains to be elucidated) allowing a prostaglandin‐mediated effect to predominate, thereby increasing muscle tone.
The influence of neonatal treatment with capsaicin on the control of blood pressure in adult rats in water‐replete and water‐deprived states
Authors: Bennett T. , Gardiner S.M. 
Published: July 2012

Arterial blood pressures and heart rates were measured in water‐replete and in water‐deprived (48 h) conscious, adult rats that had received capsaicin (50 mg kg−1) or its vehicle neonatally.
Resting arterial blood pressures and heart rates in capsaicin‐treated rats were not different from the controls in either the water‐replete or the water‐deprived state.
Inhibition of the vascular actions of vasopressin (with 1‐β‐mercapto,‐β,β‐cyclopentamethylen‐epropionic acid, 8‐D‐arginine vasopressin, (d(CH2)5DAVP)) had no significant effect on blood pressures in the water‐replete animals but caused a significant hypotension in water‐deprived rats; the magnitude of the hypotension was the same irrespective of whether the animals had received capsaicin or its vehicle.
During angiotensin converting enzyme inhibition (with captopril) and ganglion blockade (with pentolinium), the vasopressin‐mediated blood pressure recovery was more gradual in the capsaicintreated animals than in the controls, but after 60 min blood pressures were similar in all groups. Collectively the results indicate that although the full development of vasopressin‐dependent mechanisms following acute hypotension takes longer when a large proportion of unmyelinated afferent fibres have been destroyed by neonatal treatment with capsaicin, 48 h of water deprivation results in a normal involvement of vasopressin‐dependent mechanisms in the maintenance of blood pressure.
Modification of dyskinesias following the intrastriatal injection of prostaglandins in the rodent
Authors: Costall Brenda , Holmes S.W. , Kelly M. Elizabeth , Naylor R.J. 
Published: July 2012

The abilities of prostaglandin E1 (PGE1), PGE2, PGD2 and PGF2α to antagonize striatal dopamine function were assessed following bilateral and unilateral injections into the striata of the rat and guinea‐pig.
Three tests were used to assess the effects of the bilateral injections, ability to antagonize dyskinetic biting induced by 2‐di‐n‐propylamino‐5, 6‐dihydroxytetralin (0.025 mg kg‐1 s.c.), ability to antagonize stereotyped behaviour induced by apomorphine (0.5 or 2 mg kg−1 s.c.) and ability to induce catalepsy. Asymmetry/circling behaviour revealed on challenge with apomorphine (0.25 mg kg−1 s.c.) was measured following unilateral injection into the striatum.
In the rat, dyskinetic biting induced by 2‐di‐n‐propylamino‐5, 6‐dihydroxytetralin was antagonized by PGE1 (0.001 − 1 μg) and PGE2 (0.00001 − 1 μg) but not by PGD2 or PGF2α (1 μg). Stereotyped behaviour induced by apomorphine was not antagonized by any of the prostaglandins. A weak catalepsy was induced by PGE1 (1 μg only), PGE2 (0.001 − 1 μg) and PGD2 (0.001 − 1 μg) but not by PGF2α. Asymmetry and circling behaviour was only observed following the unilateral injection into the striatum of PGE1 and PGD2 (0.01 − 1 μg) and challenge with apomorphine.
In the guinea‐pig the actions of PGE1 and E2 were compared with those of PGF2α. Dyskinetic biting induced by 2‐di‐n‐propylamino‐5, 6‐dihydroxytetralin was antagonized by bilateral injections into the striatum of PGE2 (0.001 − 1 μg), but not PGE, (0.5 μg) and PGF2α (1 μg) but not PGE, (0.5 μg) and PGF2α (1 μg). Similar injections of PGE1, E2 and F2α all failed to antagonize apomorphine‐induced stereotyped behaviour, or to induce catalepsy. PGE1 (0.01‐0.5 μg) and PGE2 (0.002 − 1 μg), but not PGF2α, caused asymmetry following unilateral injection into the striatum and peripheral challenge with apomorphine.
It is concluded that the major effect in the striatum of the prostaglandins of the E series is to antagonize dyskinetic biting; this action is not shared by other prostaglandins tested, and does not reflect a generalised ability to antagonize striatal dopamine function. It is suggested that the actions of the prostaglandins to modify differentially dopamine‐dependent behaviours from the striatum may reflect activity at a site subsequent to the dopamine receptor.
Calcium‐dependent contractile response of arterial smooth muscle to a jellyfish toxin (pCrTX: Carybdea rastonii)
Authors: Azuma Hiroshi , Ishikawa Masayuki , Nakajima Terumi , Satoh Akihiko , Sekizaki Satomi 
Published: July 2012

The purpose of the present experiments was to investigate the pharmacological mechanisms of the vasoconstriction caused by the toxin (pCrTX) which had been partially purified from the tentacles of the jellyfish Carybdea rastonii (‘Andonkurage’).
pCrTX (0.1 to 10 μg ml−1) produced a tonic contraction of rabbit aortic strips, which was nearly abolished in Ca2+‐free medium and was significantly reduced by verapamil or diltiazem.
pCrTX stimulated 45Ca2+‐influx and this effect was markedly attenuated by verapamil.
pCrTX‐induced vasoconstriction was significantly attenuated by phentolamine, 6‐hydroxydopamine (6‐OHDA) and in low Na+‐medium, but not by bretylium, guanethidine, reserpinization or tetrodotoxin (TTX).
pCrTX continuously and significantly increased the 3H‐efflux from [3H]‐noradrenaline preloaded aortic strips and this effect was completely inhibited by pretreatment with 6‐OHDA and in Ca2+‐free medium, but not by phentolamine, bretylium, guanethidine or TTX.
A single exposure to pCrTX for 30 min greatly reduced the contractile responses to tyramine, nicotine and transmural electrical stimulation, but not those to noradrenaline or KCl. In addition, incorporation of [3H]‐noradrenaline was reduced.
Pretreatments with chlorphenylamine or indomethacin failed to modify the contractile response to pCrTX.
These results suggest that the pCrTX‐induced vasoconstriction is caused by a presynaptic action, releasing noradrenaline from the intramural adrenergic nerve terminals, and by a postsynaptic action, which consists at least in part of stimulation of the transmembrane calcium influx. Both pre‐ and postsynaptic actions depend on the external calcium concentration. The data further suggest that pCrTX damages the noradrenaline uptake and/or storage mechanisms without damaging postsynaptic contractile systems.
Calcium channel inhibitors suppress the morphine‐withdrawal syndrome in rats
Authors: Bongianni F. , Carla' V. , Moroni F. , Pellegrini‐Giampietro D.E. 
Published: July 2012

The effects of the Ca2+‐channel blockers verapamil and nimodipine, on the behavioural signs of naloxone (1 mg kg−1)‐induced abstinence syndrome in morphine‐dependent rats, were evaluated. The content of noradrenaline (NA) and of its metabolite 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) was measured, using high performance liquid chromatography and electrochemical detection or gas chromatography‐mass spectrometry, in various brain regions of these animals. Possible interactions of nimodipine and verapamil with opioid receptors were evaluated by examining their ability to displace [3H]‐naloxone binding to brain membranes.
Verapamil (5, 10 and 50 mg kg−1) and nimodipine (1,5 and 10 mg kg−1) dose‐dependently reduced most of the signs of morphine abstinence.
Naloxone‐precipitated abstinence decreased the NA content in the cortex, hippocampus, brainstem and cerebellum. In the same brain regions the content of MHPG increased, suggesting an increased release of the amine during morphine abstinence.
Nimodipine (10 mg kg−1 i.v.) did not change the content of NA or MHPG in the cortex, hippocampus and brainstem. However, nimodipine pre‐treatment markedly reduced the changes in NA and MHPG content induced by the abstinence syndrome.
Neither verapamil nor nimodipine displaced [3H]‐naloxone from its binding sites.
These results suggest that Ca2+‐channel blockers suppress the behavioural and neurochemical expressions of morphine abstinence by a mechanism that differs from those of opioids or α2‐adrenoceptor agonists.