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PubMed1988

Comparison of the effects of two opioid antitussives, vadocaine hydrochloride, clobutinol and lidocaine on lung mechanics in guinea-pigs.

Intravenous administration of opioids, e.g. morphine and codeine, causes bronchoconstriction in animals and susceptible patients such as asthmatics. Therefore, the effects of two opioid antitussives (codeine and dextromethorphan), two non-opioid antitussives (vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl) propionanilide hydrochloride, OR K-242-HCl; INN: vadocaine) and clobutinol), and lidocaine on basal lung mechanics and methacholine (MeCh, 6 micrograms/kg i.v.)-induced airway obstruction were investigated in anaesthetized guinea-pigs. Intravenous administration of codeine (10-20 mg/kg) produced a dual response in the airways; initial bronchoconstriction was followed by attenuation of the MeCh-response. Dextromethorphan (10 and 15 mg/kg) caused bronchoconstriction only. Both the opioids affected dynamic lung compliance (CDyn) more than lung resistance (RL). At doses between 1 and 20 mg/kg i.v., vadocaine, clobutinol, and lidocaine had no obvious effect on the airways. Dextromethorphan and vadocaine, both at doses of 10 and 15 mg/kg, and clobutinol (15 and 20 mg/kg) caused irreversible bradycardia and hypotension, whereas codeine (5-20 mg/kg) increased blood pressure, and to a lesser extent heart rate. These results suggest that intravenous administration of an opioid antitussive influences the small peripheral airways more than the large airways, whether the opioid has euphoric analgesic properties or not. In contrast to this, non-opioid antitussives such as vadocaine and clobutinol are without effect. At large doses, all antitussives influence the cardiovascular system considerably.

Amino Alcohols↗

PubMed2000

Non-NMDA receptor-mediated mechanisms are involved in levodopa-induced motor response alterations in Parkinsonian rats.

Chronic dopaminomimetic administration to parkinsonian animal models or Parkinson's disease patients leads to characteristic alteration in motor response. Previous studies suggested that the nonphysiologic stimulation of dopaminergic receptors on striatal medium spiny neurons enhances the synaptic efficacy of juxtaposed glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype. Resultant NMDA receptor sensitization due to differential changes in subunit phosphorylation appears to favor alterations in striatal output in ways that influence motor function. To detail the involvement of NMDA receptors further as well as to determine whether similar functional changes might develop in alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors, the effects of selective antagonist of AMPA receptors (6-nitro-7-sulfamoyl-benzo[f]-quinoxaline-2,3 (1H,4H)-dione sodium salt, NBQX, 10 mg/kg) on levodopa-induced response alterations in 6-hydroxydopamine (6-OHDA) lesioned rats were compared with drugs which act competitively (3-(+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonicacid, CPP, 6.25 mg/kg) or noncompetitively (dextromethorphan, 40 mg/kg) to block NMDA receptors, or a nonselective inhibitor of glutamatergic transmission (2-amino-6-trifluoromethoxy benzothiazole, riluzole, 5 mg/kg). We found that the shortened duration of the motor response to levodopa, which underlies human wearing-off fluctuations, was reversed to a similar degree by the acute coadministration of CPP, NBQX, or riluzole (n = 4-6) but dextromethorphan did not. These observations strengthen the possibility that a reduction in levodopa-associated changes in motor response by inhibitors of glutamatergic transmission acting generally or selectively at the glutamate binding-sites may relate to their ability to attenuate pathologic gain in striatal glutamatergic function. The capacity of NBQX to reverse these altered responses suggests that an enhanced synaptic efficacy of striatal AMPA receptors may also participate in the generation of these motor response changes in levodopa-treated parkinsonian rats.

Animals↗

PubMed1996

Characterization of [3H]MK-801 binding to N-methyl-D-aspartate receptors in cultured rat cerebellar granule neurons and involvement in glutamate-mediated toxicity.

The conditions required for growth and survival of cerebellar granule neurons in vitro are known to alter the developmental regulation of NMDA receptor subunit mRNA. In the present report, we have examined the functional and pharmacological characteristics of NMDA receptors on cerebellar granule neurons at 12 days in culture (12 DIC). Under open-channel conditions in extensively washed membranes, [3H]MK-801 labeled a uniform population of sites (Kd = 3.2 +/- 0.3 nM) in a saturable manner (Bmax = 416 +/- 18 fmol/mg); however, biexponential association and dissociation kinetics indicated the possible existence of at least two NMDA receptor populations that differ in pharmacological properties. The kinetically derived equilibrium dissociation constants for the high- and low-affinity binding components were 0.56 and 771 nM, respectively. The equilibrium competition analysis of MK-801 and other channel-blocking compounds as displacers of [3H]MK-801 revealed the presence of high- and low-affinity binding sites with relative apportionments of 70% and 30%, respectively. The rank-order potency profile of competitor binding at the high-affinity site was (+)-MK-801 > TCP > dextrorphan > dextromethorphan > (+)-ketamine. When tested for the ability to protect 12 DIC cerebellar granule neurons from acute glutamate-induced toxicity, the neuroprotective rank-order potency of these compounds was MK-801 > TCP > dextrorphan > (+)-ketamine > dextromethorphan, which correlated significantly with the high-affinity competition binding profile and thus established the role of NMDA receptors in glutamate toxicity. The findings of these experiments indicate that NMDA receptors on 12 DIC cerebellar granule neurons are a heterogenous population that functionally mediate glutamate-induced neurotoxicity. The heterogenous [3H]MK-801 binding sites may represent NMDA receptor channels composed of different subunits.

Animals↗

PubMed2001

Separation of cold medicine ingredients by capillary electrophoresis.

This study demonstrates the separation of cold medicine ingredients (e.g., phenylpropanolamine, dextromethorphan, chlorpheniramine maleate, and paracetamol) by capillary zone electrophoresis and micellar electrokinetic chromatography. Factors affecting their separations were the buffer pH and the concentrations of buffer, surfactant and organic modifiers. Optimum results were obtained with a 10 mM sodium dihydrogen-phosphate-sodium tetraborate buffer containing 50 mM sodium dodecyl sulfate (SDS) and 5% methanol (MeOH), pH 9.0. The carrier electrolyte gave a baseline separation of phenylpropanolamine, dextromethorphan, chlorpheniramine maleate, and paracetamol with a resolution of 1.2, and the total migration time was 11.38 min.

Acetaminophen↗

PubMed1989

Genetic predisposition to drug hepatotoxicity: role in hepatitis caused by amineptine, a tricyclic antidepressant.

Amineptine-induced immunoallergic hepatitis is unpredictable. It may be related to its oxidation into a reactive metabolite acting as hapten. We have looked for a possible genetic predisposition involving drug oxidation capacity and/or cell defense mechanisms in nine patients with previous amineptine hepatitis. Drug oxidation capacity was assessed using dextromethorphan, a test compound recently proposed as a substitute for debrisoquine. The eight patients tested had the extensive metabolizer phenotype. The susceptibility to amineptine metabolites was studied by an in vitro test assessing the destruction of the patients' lymphocytes by reactive metabolites generated from amineptine by a standardized oxidation microsomal system. Lymphocyte death increased with the dose of amineptine (1 to 2.5 mM); it was increased by preincubation with trichloropropene oxide, but was absent when amineptine was omitted or when the oxidation system was not operating. Mean lymphocyte death was twice higher in the nine patients with amineptine hepatitis than in 17 healthy controls. In contrast, when the test was performed with acetaminophen (3 to 10 mM), lymphocyte death was similar in controls and in patients. Basal epoxide hydrolase activity toward benzo[a]pyrene-4,5-oxide and glutathione concentration was similar in lymphocytes from controls and patients. Family studies showed an increased susceptibility to amineptine metabolites in lymphocytes from several first-degree relatives of two patients. These results show that amineptine hepatitis occurs in patients with extensive dextromethorphan oxidation capacity but with an increased susceptibility to amineptine reactive metabolites, probably related to a genetic deficiency in a cell defense mechanism.

Adolescent↗

PubMed1982

Determination of amine ingredients in cough-cold liquids by reversed-phase ion-pair high-performance liquid chromatography.

The chromatographic behavior of phenylephrine, codeine, pseudoephedrine, phenylpropanolamine, methoxyphenamine, pheniramine, pyrilamine, dextromethorphan, and chlorpheniramine was examined by reversed-phase, ion-pair high-performance liquid chromatography. An isocratic chromatographic system was devised for the analysis of cough-cold liquids containing these amine drugs by optimization of the mobile phase ionic strength, buffer pH, pairing ion concentration, and secondary ion concentration. Quantitative recovery and excellent precision were demonstrated for the simultaneous determination of phenylpropranolamine, dextromethorphan, and chlorpheniramine in a typical formulation. The method was successfully applied to various commercial cough-cold liquids for the analysis of a wide range of amine drugs.

Amines↗

PubMed2001

Expression, purification, and biochemical characterization of a human cytochrome P450 CYP2D6-NADPH cytochrome P450 reductase fusion protein.

Cytochrome P450 CYP2D6 metabolizes a wide range of pharmaceutical compounds. A CYP2D6 fusion enzyme (CYP2D6F), containing an amino-terminal human CYP2D6 sequence and a carboxyterminal human NADPH-cytochrome P450 oxidoreductase (CPR) moiety, was constructed. High levels of expression were achieved in Escherichia coli (60-100 nmol/liter) and the enzyme was catalytically active with optimal activities achieved in the presence of the antioxidant, GSH. Turnover values for bufuralol 1'-hydroxylation, metoprolol alpha-hydroxylation, O-desmethylation, and dextromethorphan O-demethylation, using membranes expressing the fusion enzyme, were 5.6, 0.4, 0.72, and 6.19 min(-1), respectively. These values were similar to E. coli membranes which coexpressed human CYP2D6 and CPR (CYP2D6/R). The K(m) and k(cat) values for bufuralol metabolism were estimated to be 10.2 microM and 4.1 min(-1), respectively. The enzyme was purified using ion-exchange chromatography, affinity chromatography (2'-5' ADP-Sepharose), and gel filtration. Estimated turnover rates for bufuralol 1'-hydroxylation, metoprolol alpha-hydroxylation, O-desmethylation, and dextromethorphan O-demethylation were 1.2, 0.52, 0.79, and 0.76 min(-1), respectively. Bufuralol 1'-hydroxylase activity by purified CYP2D6F was enhanced by phospholipids and added CPR. The CYP2D6F enzyme was able to stimulate CYP3A4 testosterone 6beta-hydroxylase activity in a reconstitution system indicating that electron transfer may be largely intermolecular. The catalytically self-sufficient CYP2D6F enzyme will facilitate investigations of P450-CPR interactions and the development of new biocatalysts.

Cytochrome P-450 CYP2D6↗

PubMed1988

Phenotyping polymorphic drug metabolism in the French Caucasian population.

Because of the large interethnic differences in the incidence of poor metabolizer phenotypes, French Caucasians have been studied for two independent polymorphisms, debrisoquine/dextromethorphan and mephenytoin metabolism. One hundred and thirty-two unrelated French Caucasians were phenotyped using oral doses of dextromethorphan 20 mg and mephenytoin 100 mg. Individual dextrorphan excretion over 8 h and the dextromethorphan/dextrorphan metabolic ratio were calculated. Extensive metabolizers were taken as subjects with a high dextrorphan output (15.56 mumol/8 h) and a low metabolic ratio (0.0023), and poor metabolizers were those with a low dextrorphan output (0.39 mumol/8 h) and a high metabolic ratio (7.00). Individual 4-hydroxymephenytoin excretion and mephenytoin hydroxylation indices were also determined. Extensive metabolizers eliminated large amounts of 4 hydroxymephenytoin (133.2 mumol/8 h) and had a hydroxylation index of 1.99, and poor metabolizers, because of impaired mephenytoin metabolism, had a high hydroxylation index (277). The incidence of the poor metabolizer phenotype was 3% for dextromethorphan (95% confidence limits 0.5%-8.5%) and 6% for mephenytoin (95% confidence limits 2%-12.5%).

Adult↗

PubMed2005

Identification of CYP2D6 impaired functional alleles in Mexican Americans.

OBJECTIVES: To extend the genotyping analysis of the CYP2D6 gene and further explain variability of CYP2D6 activity in Mexican Americans by genetic factors. METHODS: CYP2D6 gene sequence variations associated with *6, *7, *8, *9, *11, *14, *29, *41, *45, and *46 alleles as well as the 2988G>A SNP were examined in 264 Mexican Americans; 236 had previously been phenotyped with dextromethorphan. All subjects were previously genotyped for CYP2D6*2, *3, *4, *5, *10, *17, and the presence of a gene duplication. Associations between genotype and CYP2D6 activity were determined. RESULTS: Mexican Americans revealed a high frequency of functional alleles (CYP2D6*1 and *2; 73.1%), followed by CYP2D6*4 (non-functional, 10.0%) and the reduced-function allele *41 (9.5%). The frequencies of CYP2D6*5, *6, *9, *10, duplication, and 2988A were 1.7%, 0.4%, 1.1%, 2.8%, 0.8%, and 5.7%, respectively. CYP2D6*3, *17, and *29 were found only in one individual (CYP2D6*2/*3, *1/*17, and *4/*29), while CYP2D6*7, *8, *11, *14, *45, and *46 were absent in this study population. Decreased CYP2D6 activity was more accurately predicted by the presence *41[-1584C] compared to *41[2988A]. One genotype/phenotype discordant subject was resolved by the presence of a CYP2D6*6 allele (*4/*6), while two other cases remained discordant (*41/*41 and *1/*1). CONCLUSIONS: The CYP2D6*4, *5, and *6 null alleles along the reduced function alleles *9, *10, and *41 are the major cause for diminished dextromethorphan oxidative capacity in Mexican Americans. These findings may have implications for the safety and efficacy of CYP2D6 substrates taken by Mexican Americans.

Adult↗

PubMed1996

Interindividual variability in catalytic activity and immunoreactivity of three major human liver cytochrome P450 isozymes.

OBJECTIVE: Interindividual variations in immunoreactivity and function of three major human drug metabolising P450 monooxygenases has been investigated in liver microsomes from 42 Caucasians (kidney donors or liver biopsies). METHODS: Diclofenac 4'-hydroxylation, dextromethorphan O-demethylation and midazolam 1'-hydroxylation, measured by HPLC in incubates, were used as probes to determine CYP2C9, CYP2D6 and CYP3A4 function kinetics, respectively. Immunoquantification of the three isoforms was achieved by Western blotting, using rabbit polyclonal antibodies raised against human CYP2C9 and human CYP3A4, and mouse monoclonal antibody raised against human CYP2D6. RESULTS: Diclofenac 4'-hydroxylation exhibited Michaelis-Menten kinetics with kM = 3.4 mumol.l-1 and Vmax = 45 nmole.mg-1 P.h-1. Relative immunoreactivity of CYP2C9 was correlated with Vmax and CL(int). Dextromethorphan O-demethylation in EM (extensive metabolisers) liver microsomes also showed Michaelis-Menten kinetics, with kM = 4.4 mumol.l-1 and Vmax = 5.0 nmol.mg-1 P.h-1. Relative immunoreactivity of CYP2D6 was correlated with Vmax and CL(int). Midazolam 1'-hydroxylation also exhibited Michaelis-Menten kinetics with kM = 3.3 mumol.l-1 and Vmax = 35 nmol.mg-1 P.h-1. Relative immunoreactivity of CYP3A4 was correlated with Vmax and CL(int). Immunoreactivity and function were correlated for each isozyme, but there was no cross correlation between isozymes. CONCLUSION: The velocity of metabolite formation (Vmax) by the three major human drug metabolising P450 monoxygenases is correlated with their immunoreactivity in liver microsomes. Interindividual variation was much larger for Vmax than kM. Interindividual variability was more pronounced for CYP2D6, probably due to the presence of several different functional alleles in the population of extensive metabolisers.

Adult↗

PubMed1975

A new method for evaluating antitussives in cats using an electrode-cannula.

An emplaced laryngo-tracheal electrode-cannula was employed to induce and to measure cough in cats anesthetized with either sodium pentobarbital or Dial--urethane. Carbetapentane citrate, codeine sulfate and dextromethorphan hydrobromide were tested for antitussive action by this method. Relative antitussive potency obtained in order of decreasing effectiveness was dextromethorphan hydrobromide, codeine sulfate and carbetapentane citrate.

Animals↗

PubMed1991

[3H]DTG and [3H](+)-3-PPP label pharmacologically distinct sigma binding sites in guinea pig brain membranes.

The interaction of various compounds with sigma binding sites was examined in membranes prepared from whole guinea pig brain. Whereas [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine labeled a single population of binding sites exhibiting a Kd of 43 nM, [3H]1,3-di-o-tolylguanidine bound to two sites having Kds of 35 and 212 nM, and to a greater maximum number of sites than [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine. Haloperidol, 1,3-di-o-tolylguanidine, BMY 14802, and (-)-pentazocine each displayed nearly equal affinity for binding sites labeled by [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine and [3H]1,3-di-o-tolylguanidine, whereas (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine was 3 times more potent in inhibiting [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine than [3H]1,3-di-o-tolylguanidine binding. In contrast, (+)-SKF 10,047, (+)-cyclazocine and (+)-pentazocine exhibited more than 9-fold higher affinity for [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine than [3H]1,3-di-o-tolylguanidine binding sites. Dextromethorphan was 15-fold more potent against [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine than [3H]1,3-di-o-tolylguanidine, inhibited [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine binding in a biphasic manner, and inhibited [3H]haloperidol and [3H](+)-SKF 10,047 binding with potencies similar to those obtained against [3H]1,3-di-o-tolylguanidine and [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine, respectively. Phenytoin increased [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine and [3H](+)-SKF 10,047 binding, but did not enhance [3H]1,3-di-o-tolylguanidine or [3H]haloperidol binding. However, the potency of dextromethorphan to inhibit [3H]1,3-di-o-tolylguanidine binding was increased in the presence of phenytoin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Two subtypes of enteric non-opioid sigma receptors in guinea-pig cholinergic motor neurons.

In the longitudinal muscle-myenteric plexus preparation (LMMP) of the guinea-pig ileum, the non-opioid sigma receptors agonists, 1,3-di-ortho-tolylguanidine (DTG) and (+)N-allyl-N-normetazocine [(+)SKF 10,047], had opposite effects on nerve-mediated cholinergic contractions caused by electrical field stimulation. DTG (0.1-10 microM) inhibited and (+)SKF 10,047 (0.1-10 microM) markedly enhanced these contractile responses. Both effects were evaluated in the presence (0.5 or 1 microM) of the putative antagonists at central sigma sites: haloperidol, rimcazole, BMY 14802 and dextromethorphan. Haloperidol and dextromethorphan were ineffective. Rimcazole antagonized the effect of both DTG and (+)SKF 10.047. BMY 14802 antagonized the (+)SKF 10.047-mediated excitatory response only. These results suggest that two sigma receptor subtypes are present in enteric cholinergic motor neurons innervating the longitudinal coat. Rimcazole and BMY 14802 may provide useful tools for the characterization of peripheral non-opioid sigma receptors.

Animals↗

PubMed1993

Effects of rimcazole, a specific antagonist of sigma sites, on the antitussive effects of non-narcotic antitussive drugs.

We examined the effects of rimcazole, a specific antagonist of sigma sites, on the antitussive effects of dextromethorphan and noscapine in mice. Intraperitoneal injection of rimcazole, in doses from 1 to 10 mg/kg, significantly and dose dependently antagonized the cough depressant effect of N,N'-di(orthotolyl)guanidine (DTG), a sigma ligand. The cough depressant effects of dextromethorphan (3 mg/kg i.p.) and noscapine (10 mg/kg i.p.) were also significantly and dose dependently reduced by pretreatment with rimcazole. However, rimcazole (10 mg/kg i.p.) did not have a significant effect on the antitussive effect of morphine (3 mg/kg i.p.). Furthermore, rimcazole by itself (10 and 30 mg/kg i.p.) had no significant effect on the number of coughs. These results suggest that sigma sites may be involved in the antitussive mechanism of centrally acting non-narcotic antitussive drugs.

Animals↗

PubMed1994

Effects of haloperidol and reduced haloperidol on binding to sigma sites.

The s.c. administration of a single dose of 0.1 mg/kg of reduced haloperidol to guinea pigs produced a marked inhibition of the binding of [3H]dextromethorphan and [3H]3-(3-hydroxyphenyl)-N-(n-propyl)piperidine ([3H](+)-3-PPP) to brain. The inhibition was still evident 10 days later, and it was accompanied by residual brain levels of reduced haloperidol, and much lower levels of haloperidol. Scatchard and computer-assisted analysis demonstrated that the inhibition was due to a reduction in the number of binding sites without changes in the affinity. In the rat, haloperidol and reduced haloperidol also produced a rapid inhibition of binding to sigma sites. Interestingly, the brain of the reduced haloperidol-treated rats contained both haloperidol and reduced haloperidol, but the levels of reduced haloperidol in the haloperidol-treated rats were undetectable. However, the inhibition observed was of comparable magnitude, indicating that the haloperidol remaining in the brain is also inhibitory. In vitro experiments showed that the inhibition produced by haloperidol and reduced haloperidol was apparently competitive, but when brain membranes were preincubated with either drug, the inhibition was noncompetitive. By contrast, the inhibition produced by dextromethorphan was always competitive. Moreover, the inhibition produced by haloperidol and reduced haloperidol could not be reversed by washing. This investigation strongly suggests that the inhibition observed after the administration of haloperidol or reduced haloperidol is not a classic agonist-induced receptor down-regulation. The results indicated that the inhibition produced is a complex phenomenon, and suggest the formation of a slowly reversible or irreversible complex with reduced haloperidol or haloperidol.

Animals↗

PubMed1983

Further evidence for a motility substitution test as a tool to detect the narcotic character of new drugs in rats.

Time effects of three doses of codeine, d-propoxyphene, meperidine and dextromethorphan upon locomotor activity have been investigated in naive rats as well as in animals treated chronically with 20 mg/kg of morphine daily. The first three drugs exhibited a motility pattern qualitatively similar to that of morphine; in chronically-treated rats cross-tolerance occurred to acute depressant effects and cross-sensitization to acute excitatory effects. In the case of meperidine however cross-sensitization appeared to be small. Dextromethorphan presented effects similar to morphine only in a very large dose. The present data, together with those of previous work, demonstrate that a locomotor activity substitution test may predict the morphine-like addictive properties of a drug.

Animals↗

PubMed1991

Previous chronic blockade of NMDA receptors intensifies morphine dependence in rats.

Chronic exposure of receptors to antagonists generally results in upregulation and/or supersensitivity. On the other hand, the noncompetitive NMDA receptor antagonists ketamine (K) and dextromethorphan (DM) suppress opiate abstinence syndrome by blocking NMDA receptors. Therefore, 40 mg/kg ketamine (K), 5 mg/kg dextromethorphan (DM), 5 mg/kg morphine (M) and 2 mg/kg naloxone (NL) alone or in combination with NL were IP administered to the rats five times during the daytime only for five days to see whether they would intensify abstinence syndrome through upregulation and/or supersensitivity of NMDA receptors. Three days following the implantation of three M-containing pellets, abstinence syndrome was brought about by 2 mg/kg NL injection. Jumping, wet dog shake, writhing, teeth chattering, diarrhoea, defecation and ptosis were observed for ten min. All drugs used alone or in combination with NL increased the intensity of abstinence syndrome. Since K and DM are noncompetitive NMDA receptor antagonists, the intensifying effect of NL or M was considered to be related to their interactions with NMDA receptors. Furthermore, on the basis of the results of the previous and present study, NL was claimed to act on NMDA receptors, like other opioids, but with higher affinity for and weaker blocking effect on NMDA receptors.

Amino Acids↗

PubMed1992

Sigma ligand-induced emesis in the pigeon.

Pigeons were fed a fixed amount of grain-based feed and behavior was observed after administration of doses of ditolyguanidine (DTG), (+)-3-(3-hydroxyphenyl)-N-(1-propyl)-piperidine [(+)-3-PPP], dextromethorphan, haloperidol, (+)-N-allylnormetazocine (NANM), alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-butanol (BMY-14802) apomorphine, pentobarbital, propranolol, and MK-801. Of the drugs tested, DTG, dextromethorphan, and (+)-3-PPP each produced dose-related increases in the percentage of pigeons exhibiting an emetic response. The emetic response produced by DTG was antagonized by haloperidol and BMY-14802 but not by propranolol. These observations suggest that the emetic response in the pigeon may be mediated by sigma sites and is unlikely to be mediated by phencyclidine receptors.

Animals↗