Biomedical subjects

N M Barnes

Publications and source records attributed to N M Barnes.

At least 55 records · Page 3Linked to original sources

PubMed1993

A comparison of rat brain amino acid and monoamine content in diazepam withdrawal and after exposure to a phobic stimulus.

1. The content of amino acids (taurine, glycine, glutamic acid, gamma-aminobutyric acid (GABA) and aspartic acid) and monoamines (5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline) in homogenates of rat cortical and hippocampal tissue were measured by high performance liquid chromatography (h.p.l.c.) with fluorescent and electrochemical detection respectively, after two anxiogenic treatments: exposure to a phobic stimulus (cat odour) and withdrawal from chronic diazepam treatment. 2. In neither of the two anxiogenic situations was there a significant change in any amino acid content, in either brain area. 3. In the group withdrawn from chronic diazepam, cortical 5-HT and 5-HIAA levels and hippocampal 5-HT levels were significantly increased. Noradrenaline content was significantly decreased in the hippocampus. 4. The changes in 5-HT and 5-HIAA levels following cat odour exposure were area-specific in that they decreased in the hippocampus, but increased in the cortex. 5. Following cat odour exposure, noradrenaline levels appeared not to change in either area studied. However during exposure to cat odour, it was found that half the animals avoided the odour source and half were indifferent. The animals showing marked avoidance had significantly higher cortical noradrenaline content and this was significantly different from control, whereas hippocampal noradrenaline levels were not dependent upon the differences in avoidance of the odour source. 6. The results show clearly different neurochemical changes in the rat following exposure to a phobic stimulus and withdrawal from diazepam. It is hoped comparative studies such as this will enable better understanding of anxiety states in the rat which could parallel the different classes of anxiety recognised in the clinic

Amino Acids↗

PubMed1992

The interaction of R(+)- and S(-)-zacopride with PCPA to modify rodent aversive behaviour.

The interaction of R(+)- and S(-)zacopride (0.00001-10 mg/kg i.p.) with parachlorophenylalanine (PCPA, 3 day treatment 100 mg/kg i.p.) to modify behaviour in an aversive situation was investigated in the mouse black and white test box and rat social interaction test. R(+)-Zacopride (but not S(-)zacopride) and PCPA had an anxiolytic profile of action to reduce aversive responding in both species. Their established anxiolytic profiles were abolished by a subsequent treatment with S(-)zacopride. In contrast, S(-)-zacopride was less or ineffective if administered simultaneously with R(+)-zacopride. A co-treatment of PCPA with R(+)-zacopride also inhibited the anxiolytic profiles observed to the individual treatments. It is concluded that there is a complex interaction between the isomers of zacopride to modify responding to an aversive situation that is dependent on the temporal sequence of drug administration, and which may be modified by changes in basal 5-hydroxytryptamine (5-HT) tone and agonist, partial agonist and antagonist effects at the 5-HT3 receptor.

Animals↗

PubMed1992

Profiles of interaction of R(+)/S(-)-zacopride and anxiolytic agents in a mouse model.

The mouse black and white test box was used to measure changes in behaviour in an aversive situation where the administration of R(+)-zacopride (but not S(-)-zacopride) alone decreased aversive responding to the white area. A similar anxiolytic profile of action was observed using parachlorophenylalanine (PCPA), whose effects were antagonised by a co-treatment with R(+)-zacopride and reversed by S(-)-zacopride to an exacerbation of the aversive response. An anxiolytic profile of action was also observed using ondansetron, granisetron, chlordiazepoxide, diazepam, ritanserin, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), E4424 (2-[4-[4-(4-chloro-l-pyrazoyl)butyl]-l-piperazinyl]-pyrimidine), umepsirone, DuP753 (2-n-butyl-4-chloro-5-hydroxy-methyl-1-[2(1H-tetrazol-5-yl) biphenyl-4-yl)methyl)]-imidazole), SQ29,852 ((S)-1-[6-amino-2[hydroxy)(4-phenyl-butyl)phosphinyl]-oxy)-1- nexy]-2-proline), devazepide and guanfacine, and this was retained following co-treatment with PCPA. The anxiolytic profile of action of PCPA was also retained following co-treatment with renzapride which when administered alone failed to modify behaviour. However, the ability of chlordiazepoxide, diazepam, ondansetron and E4424 (but not devazepide, DuP753 or SQ29,852) to reduce aversive responding was inhibited by co-treatment with R(+) and/or S(-)-zacopride. It is concluded that the reduction in aversive responding caused by pharmacological manipulation at the benzodiazepine, 5-HT receptor subtypes 5-HT1A, 5-HT1C/5-HT2 and 5-HT3 (but not at the cholecystokin CCKA or angiotensin receptors or inhibition of angiotensin converting enzyme) can be inhibited by R(+) and S(-)-zacopride. The data is discussed in terms of zacopride having an agonist or partial agonist effect at the 5-HT3 receptor.

Animals↗

PubMed1992

The distribution of 5-HT3 recognition sites in the marmoset brain.

The distribution of the binding of [3H]GR65630 (0.2 nM) to putative 5-HT3 recognition sites in the brain of the common marmoset was assessed using autoradiography. Specific binding was heterogeneously distributed with the highest densities found in discrete nuclei of the lower medulla (nucleus tractus solitarii, dorsal motor nucleus of the vagus nerve, nucleus of spinal trigeminal nerve tract and the area postrema). In forebrain areas, relatively high binding densities were located in the medial habenula nucleus and the hippocampus (CA3, CA4 and fascia dentata). Low levels of specific binding in the rest of the forebrain hindered quantification.

Animals↗

PubMed1992

Pharmacological comparison of the rat and guinea-pig cortical high affinity 5-hydroxytryptamine uptake system.

The pharmacological characteristics of the high affinity [3H]5-hydroxytryptamine ([3H]5-HT) uptake system were investigated in the cerebral cortex of the rat and guinea-pig. In crude cortical synaptosomal preparations from the rat and guinea-pig, [3H]5-HT accumulated with high affinity (Km, 72 +/- 12 and 57 +/- 14 nM for rat and guinea-pig cortical synaptosomal preparation, respectively, mean +/- SEM, N = 5) and with a comparable maximum activity (Vmax, 1.22 +/- 0.21 and 0.90 +/- 0.19 pmol/min/mg protein for rat and guinea-pig cortical synaptosomal preparation, respectively, mean +/- SEM, N = 5). Competition studies employing a range of structurally diverse competing compounds showed that the [3H]5-HT uptake was pharmacologically similar in both preparations. However, citalopram possessed approximately 10-fold weaker affinity to prevent [3H]5-HT uptake in the guinea-pig preparation when compared to the rat and all of the tricyclic antidepressants assessed in the present studies (amitriptyline, nortriptyline, desipramine and imipramine) displayed higher affinity in the guinea-pig preparation when compared to the rat. It is concluded that the high affinity 5-HT uptake systems in the rat and guinea-pig cortex are similar but may not be identical.

Amitriptyline↗

PubMed1992

Pharmacological comparison of the sigma recognition site labelled by [3H]haloperidol in human and rat cerebellum.

The radioligand binding characteristics of [3H]haloperidol (in the presence of spiperone, 25 nmolL-1) were investigated in rat and human cerebellar membranes. In both rat and human cerebellar membrane preparations saturation studies with [3H]haloperidol (non-specific binding defined by pentazocine, 10 mumolsL-1) demonstrated high affinity saturable specific binding to a homogenous population of binding sites (rat, Bmax 6693 +/- 1242 fmol mg-1 protein, pKD 8.33 +/- 0.08; human, Bmax 2550 +/- 437 fmol mg-1 protein, pKD 8.59 +/- 0.11; mean +/- SEM, n = 3-6). Competition studies employing a wide range of structurally diverse competing compounds displayed that the [3H]haloperidol binding site was pharmacologically similar in both preparations and comparable to sigma recognition sites previously identified in various tissues originating from different species. In addition, with reference to the potential subtypes of sigma recognition sites, the labelling of these sites by low nanomolar concentrations of [3H]haloperidol provides evidence that they belong to the sigma-1 recognition site subtype. The present findings suggest that the pharmacology of the rat and human cerebellar sigma recognition site are directly comparable and provides further supporting evidence towards the use of [3H]haloperidol radioligand binding studies in the rat to detect sigma receptor ligands with potential therapeutic activity.

Animals↗

PubMed1992

Behavioural pharmacology of 5-HT3 receptor ligands.

Extensive studies have ascribed a role for the central 5-HT3 receptor in the modulation of behaviour. Much of the work stems from the actions of potent and selective 5-HT3 receptor antagonists; these agents reduce mesolimbic dopamine initiated hyperactivity, release suppressed behaviour, reduce the reinforcing properties and withdrawal symptoms of drugs of abuse, enhance cognitive performance and modulate appetite. This article reviews the preclinical and clinical evidence implicating the 5-HT3 receptor in these indications and discusses the potential neurochemical mechanisms underlying the behavioural changes.

Animals↗

PubMed1992

Anxiolytic-like actions of anpirtoline in a mouse light-dark aversion paradigm.

The anxiolytic-like potential of anpirtoline was assessed in a mouse light/dark aversion test. Anpirtoline (1.0 ng kg(-1)-1.0 micrograms kg-1 i.p.) reduced the aversive responding of mice. This was detected as an increase in the latency to locate the non-aversive compartment and by decreases in the percentage of the time spent in the dark compartment, and the numbers of rears and line crossings in the dark compartment. In radioligand binding studies anpirtoline displayed submicromolar affinity for 5-HT1A, 5-HT1B and 5-HT3 receptor recognition sites (Ki = 151, 28 and 30 nM, respectively) and more modest affinity for 5-HT2 receptor recognition sites (Ki = 1.48 microM). It is concluded that anpirtoline has a unique spectrum of affinity for 5-HT receptor subtypes, its interaction with which may account for its anxiolytic-like activity.

Animals↗

PubMed1992

Angiotensin-converting enzyme inhibition, angiotensin, and cognition.

In these studies, we have investigated possible cognition-enhancing effects of angiotensin-converting enzyme (ACE) inhibition, and putative neurochemical correlates for these actions. In a mouse habituation model, ACE inhibitors improved basal performance and antagonized scopolamine-induced deficits. The performance of aged mice and those with lesions of the nucleus basalis was also improved. ACE inhibition also improved scopolamine-impaired performance of rats in a swim-maze model. Neurochemical studies showed that a low dose (10 micrograms/kg i.p.) of ceranapril caused significant alterations in ex vivo rat brain catecholamine levels in the nucleus accumbens, amygdala, and septum. In further studies, angiotensin II (Ang II) was shown to decrease potassium-stimulated [3H] acetylcholine release from slices of rat entorhinal and human temporal cortex, an effect that could be antagonized by the angiotensin receptor antagonist [1-sar,8-thr]Ang II. It is concluded that ACE inhibition can improve both basal and impaired performance in animal models of learning, and that this improvement may be in part a consequence of the removal by ACE inhibition of an inhibitory tone on central acetylcholine release, and/or an effect on central catecholaminergic function.

Acetylcholine↗

PubMed1992

Agonist interactions with 5-HT3 receptor recognition sites in the rat entorhinal cortex labelled by structurally diverse radioligands.

1. The pharmacological properties of 5-HT3 receptor recognition sites labelled with [3H]-(S)-zacopride, [3H]-LY278,584, [3H]-granisetron and [3H]-GR67330 in membranes prepared from the rat entorhinal cortex were investigated to assess the presence of cooperativity within the 5-HT3 receptor complex. 2. In rat entorhinal cortex homogenates, [3H]-(S)-zacopride, [3H]-LY278,584, [3H]-granisetron and [3H]-GR67330 labelled homogeneous densities of recognition sites (defined by granisetron, 10 microM) with high affinity (Bmax = 75 +/- 5, 53 +/- 5, 92 +/- 6 and 79 +/- 6 fmol mg-1 protein, respectively; pKd = 9.41 +/- 0.04, 8.69 +/- 0.14, 8.81 +/- 0.06 and 10.14 +/- 0.04 for [3H]-(S)-zacopride, [3H]-LY278,584, [3H]-granisetron and [3H]-GR67330, respectively, n = 3-8). 3. Quipazine and granisetron competed for the binding of each of the radioligands in the rat entorhinal cortex preparation at low nanomolar concentrations (pIC50; quipazine 9.38-8.51, granisetron 8.62-8.03), whilst the agonists, 5-hydroxytryptamine (5-HT), phenylbiguanide (PBG) and 2-methyl-5-HT competed at sub-micromolar concentrations (pIC50; 5-HT 7.16-6.42, PBG 7.52-6.40, 2-methyl-5-HT 7.38-6.09). 4. Competition curves generated with increasing concentrations of quipazine, PBG, 5-HT and 2-methyl-5-HT displayed Hill coefficients greater than unity when the 5-HT3 receptor recognition sites in the entorhinal cortex preparation were labelled with [3H]-LY278,584, [3H]-granisetron and [3H]-GR67330. These competing compounds displayed Hill coefficients of around unity when the sites were labelled with [3H]-(S)-zacopride. Competition for the binding of [3H]-(S)-zacopride, [3H]-LY278,584, [3H]-granisetron and [3H]-GR67330 by granisetron generated Hill coefficients around unity.5. The nature of the interaction of competing compounds (quipazine, granisetron, PBG, 5-HT, 2-methyl-5-HT) for the [3H]-(S)-zacopride binding site in the rat entorhinal cortex preparation was not altered by the removal of the Krebs ions or the addition of the monoamine oxidase inhibitor, pargyline, to the HEPES/Krebs buffer.6. In conclusion, the present studies provide further evidence towards the presence of cooperativity within the 5-HT3 receptor macromolecule and indicate that either [3H]-(S)-zacopride labels a different site on the receptor complex from [3H]-LY278,584, [3H]-granisetron or [3H]-GR67330, or it binds in such a manner as to prevent the conformatory change in the receptor protein responsible for the cooperative binding of agonists (and quipazine).

Animals↗

PubMed1992

Differential modulation of extracellular levels of 5-hydroxytryptamine in the rat frontal cortex by (R)- and (S)-zacopride.

1. The ability of various anxiolytic and potential anxiolytic agents to modify 5-hydroxytryptamine (5-HT) release in the frontal cortex of the rat was assessed by the microdialysis technique. 2. The benzodiazepine receptor agonist, diazepam (2.5 mg kg-1, i.p.), the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.32 mg kg-1, s.c.) and the 5-HT1A receptor partial agonist buspirone (4.0 mg kg-1, i.p.) maximally reduced extracellular levels of 5-HT in the rat frontal cortex by approximately 50-60%, 70-80% and 30-40%, respectively. 3. (R)-zacopride (1.0-100 micrograms kg-1, i.p.) dose-dependently reduced extracellular levels of 5-HT in the rat frontal cortex (approximately 80% maximal reduction) whereas the other 5-HT3 receptor antagonists ondansetron (10 micrograms kg-1, i.p.) and (S)-zacopride (10-100 micrograms kg-1, i.p.) were ineffective. 4. In contrast to (S)-zacopride (100 nM; administered via the microdialysis probe), (R)-zacopride (1.0-100 nM; administered via the microdialysis probe) induced a concentration-dependent reduction in extracellular levels of 5-HT in the rat frontal cortex (approximately 70% maximal reduction). 5. In contrast to ondansetron (100 micrograms kg-1, i.p.), (S)-zacopride (10-100 micrograms kg-1, i.p.) dose-dependently reversed the (R)-zacopride (10 micrograms kg-1, i.p.) induced reduction in extracellular levels of 5-HT in the rat frontal cortex. The highest dose of (S)-zacopride (100 micrograms kg-1, i.p.) completely prevented the (R)-zacopride response.In addition, (S)-zacopride (100 nM; administered via the microdialysis probe) attenuated the inhibitory action of (R)-zacopride (10 nM; administered via the microdialysis probe) on extracellular levels of 5-HT in the rat frontal cortex.6. In conclusion, the present study provides further evidence of the ability of diazepam, 8-OH-DPAT and buspirone to reduce the activity of the central 5-hydroxytryptaminergic system in vivo. Furthermore,the results indicate that the ability of (R)-zacopride to reduce the in vivo release of 5-HT in the rat frontal cortex does not correlate with its 5-HT3 receptor antagonism. However, the differential affinity of (R)- and (S)-zacopride for a (S)-zacopride-insensitive (R)-zacopride site in rat cerebral cortex mirrors the relative activity of the two zacopride stereoisomers to modify the in vivo release of 5-HT in the frontal cortex of the rat and their ability to release suppressed behaviour in animal models of anxiety.

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

PubMed1991

Angiotensin converting enzyme density is increased in temporal cortex from patients with Alzheimer's disease.

The present study assesses the binding density of the selective angiotensin converting enzyme (ACE) radioligand [3H]ceranapril in brain tissue homogenates derived from patients with Alzheimer's disease and those from age-, sex- and post-mortem delay-matched neurologically normal patients. Saturation studies with [3H]ceranapril identified that the specific binding (defined by captopril, 10 microM) was homogenous and of high affinity. ACE inhibitor recognition site density was higher by some 70% in the temporal cortex (Brodmann area 22) from Alzheimer's patients whereas densities were similar in frontal cortex and cerebellum when compared to control tissue. It is unknown whether this apparently selective alteration in ACE density is directly related to, or a compensatory effect of the disease, but it provides additional support for the development of compounds which interact with the central angiotensin system as novel therapies for cognitive dysfunction.

Aged↗

PubMed1991

Characterisation of [3H]ceranapril recognition sites in rat and human brain tissue.

The present studies assessed the nature of the recognition site for [3H]ceranapril in tissue from rat and human brain. [3H]Ceranapril exhibited high affinity saturable specific (defined by 1 microM captopril) binding to homogenates of tissue from both rat and human brain (mean pKd values between 8.42 and 8.69). High binding densities were observed in rat striatum and homogenates of tissue from human caudate (Bmax values 3317 +/- 192 and 1900 +/- 110 fmol/mg protein respectively), with comparatively low densities in cortical tissues. In kinetic experiments, association of [3H]ceranapril to homogenates of rat and human cortex was found to be rapid and fully reversible (K+1 = 6 x 10(5) M-1 sec-1 and 2.4 x 10(6) M-1 sec-1, K-1 = 7.6 x 10(-3) sec-1 and 4.5 x 10(-3) sec-1 respectively). In competition studies, lisinopril, captopril, unlabelled ceranapril, epicaptopril and fosinopril, all competed to a similar extent and with similar rank order of potency for the binding of [3H]ceranapril to homogenates of both rat and human brain. In in vivo studies, pretreatment of rats with either captopril or lisinopril (15 micrograms/250 g) significantly reduced the content of tritium in brain, as measured 20 min after intravenous administration of [3H]ceranapril. From these experiments [3H]ceranpril appears to selectively label, with high affinity, the inhibitor binding site of angiotensin converting enzyme and this site appears to be similar in both species studied.

Adult↗

PubMed1991

The actions of fentanyl to inhibit drug-induced emesis.

The ability of fentanyl to inhibit drug-induced emesis was investigated in the ferret. Initial studies established that morphine, in small doses (0.025-0.5 mg/kg s.c.), induced emesis in the ferret that decreased at the larger doses of 1 and 2 mg/kg (s.c.). Fentanyl (10-80 micrograms/kg s.c.) failed to induce emesis but in this dose range prevented the emesis induced by morphine (0.5 mg/kg s.c.), apomorphine (0.25 mg/kg s.c.), copper sulphate (100 mg/kg intragastric) and cisplatin (10 mg/kg i.v.). The antiemetic effects could be obtained in the absence of sedation or motor impairment. The antagonism by fentanyl of apomorphine-, copper sulphate- and cisplatin-induced emesis was inhibited by naloxone (0.1 or 0.5 mg/kg s.c.). It is concluded that fentanyl exerts a broad spectrum of actions to inhibit drug-induced emesis. An autoradiographic study of the binding of [3H]DAGO to the brainstem of the ferret indicated high densities of mu recognition sites in the area postrema, nucleus tractus solitarius, dorsal motor nucleus of the vagus, reticular medulla and other sites. The results are discussed in terms of balanced facilitatory and inhibitory opioid systems, regulating emesis and that the antiemetic actions of fentanyl reflect an important, although not necessarily an exclusive, action at mu opioid receptors.

Animals↗

PubMed1991

The effects of umespirone as a potential anxiolytic and antipsychotic agent.

Umespirone was compared to buspirone, diazepam and clozapine as a potential anxiolytic and antipsychotic agent. In the mouse black and white test box, umespirone was considerably more potent than diazepam or buspirone to reduce aversive responding, tolerance to its effects was not observed and sedation was absent, a chronic treatment and withdrawal was not associated with an anxiogenic profile, and umespirone prevented the behavioural consequences of withdrawal from diazepam. Umespirone also had an anxiolytic profile of action in the tests of rat social interaction and in the marmoset exposed to a human threat. Both umespirone and clozapine reduced the hyperactivity induced by the infusion of dopamine into the nucleus accumbens of rat. In radioligand binding assays umespirone demonstrated nanomolar affinity for the alpha 1-adrenoceptor and the 5-HT1A and dopamine D2 receptors. It is concluded that umespirone may present as a novel psychotropic agent with anxiolytic and antipsychotic potential.

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

PubMed1991

Cognitive enhancing actions of PD123177 detected in a mouse habituation paradigm.

The anxiolytic-like and cognitive enhancing potential of PD123177, a non-peptide with selectivity for the angiotensin II-2 receptor recognition site, was assessed in a mouse light/dark aversion test and habituation test, respectively. PD123177 (0.01 ng kg-1 to 1.0 mg kg-1 i.p.) failed to alter the behavioural repertoire of animals in the light/dark aversion test. In contrast, daily administration of PD123177 (10.0 ng kg-1 i.p. b.d.) enhanced the performance of mice in a habituation test. In addition, PD123177 overcame the cognitive impairment induced by the administration of scopolamine (0.25 mg kg-1 i.p.). Such findings indicate for the first time a functional role for the angiotension II-2 receptor and further implicate the angiotensin system in the modulation of cognitive processes.

Angiotensin II↗

PubMed1991

Identification of angiotensin II receptor subtypes in human brain.

The present study assessed the binding characteristics of [125I]angiotensin II to slices of human cerebellum adhered to glass slides using quantitative receptor autoradiography. Specific [125I]angiotensin II binding, defined by the inclusion of unlabelled angiotensin II (1.0 microM), was detected in the molecular layer of the cerebellum (0.09 +/- 0.02 fmol/mg tissue equivalent, mean +/- s.e.m., n = 3). The angiotensin II-2 receptor subtype selective ligand, PD123177, competed for approximately 65% of the specific binding in the molecular layer whilst the remainder of the specific binding was displaced by the angiotensin II-1 receptor subtype selective ligand, DuP753. It is concluded that angiotensin II receptor subtypes exist in human brain tissue and provide potential therapeutic sites of action.

Aged↗

PubMed1990

Identification and distribution of 5-HT3 recognition sites within the human brainstem.

The present studies demonstrate the presence of specific [3H]GR65630 binding sites within the human brainstem using the techniques of in vitro receptor autoradiography and ligand binding to homogenates. Autoradiography revealed the greatest accumulation of specific binding in the area postrema and subpostrema (AP/ASP). A lower level of specific binding was identified in the nucleus tractus solitarius (excluding area subpostrema). No specific binding was evident in the remainder of the hindbrain at this level. Discrete dissection followed by ligand binding to homogenates revealed that the specific binding of [3H]GR65630 (defined by the presence of 30 microM metoclopramide) was differentially distributed with highest levels in the AP/ASP (112.1 fmol/mg protein) and lower levels in the dorsal vagal complex (nucleus tractus solitarius--excluding the area subpostrema--dorsal motor nucleus of the vagus and hypoglossal nucleus) (DVC) and olivary nucleus (ON) (22.9 and 3.9 fmol/mg, respectively). No specific binding was detectable in the reticular formation (RF) located ventral to the dorsal vagal complex. The specific [3H]GR65630 binding site was pharmacologically similar to the 5-HT3 receptor since the potent and selective 5-HT3 receptor antagonists ICS 205-930 and zacopride (100 nM) and the agonist 5-HT (10 microM) inhibited binding to the same extent as metoclopramide in each of the individual areas (90, 60 and 20% in the AP/ASP, DVC and ON, respectively). The 5-HT1-like and 5-HT2 receptor antagonist methysergide (10 microM) failed to compete for the binding site. 5-HT3 receptor recognition sites within the AP/ASP and the DVC may be functionally involved in the ability of 5-HT3 receptor antagonists to control emesis.

Adult↗