Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2-Chloro-11-(2-dimethyl-aminoethoxy)dibenzo [b,f]thiepine (zotepine) is a new neuroleptic drug with a chemical structure different from known neuroleptics. The psychopharmacological effects of zotepine in mice, rats and dogs were studied and compared with those of commercially available neuroleptics. Haloperidol and perphenazine were the most active and thioridazine was the least active in hibiting apomorphine-induced gnawing and circling movement, methamphetamine-induced gnawing and circling movement, conditioned avoidance response, motor activity, dopamine-induced pancreatic secretion and apomorphine-induced vomiting. These drugs also had the same order of potency in inducing catalepsy and increasing dopamine turnover and prolactin release. Chlorpromazine, propericiazine and thiothixene were intermediate in potency. Zotepine equalled chlorpromazine in most activities, however, it was clearly less active than chlorpromazine in potentiation of barbiturate sleep and cardiovascular effect.
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PMID:Pharmacological study of [2-chloro-11-(2-dimethylaminoethoxy) dibenzo[b,f]thiepine] (zotepine), a new neuroleptic drug. 4 13

Pharmacological and biochemical properties of a novel compound, N-(1-benzyl-3-pyrrolidinyl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-08050) were compared with those of haloperidol (HPD) and chlorpromazine (CPZ) in animals. YM-08050 was more potent than either HPD or CPZ in inhibitory effects on a variety of behaviors such as apomorphine-induced stereotypes behavior and emesis, methamphetamine-induced stereotyped behavior, conditioned avoidance response and open field behavior. YM-08050 induced catalepsy only at much higher doses than to exhibit the inhibitory activities. The inhibitory effects of YM-08050 on [3H]dopamine binding and dopamine-sensitive adenylate cyclase in the synaptic membrane fractions of canine caudate nucleus were much greater than those of HPD and CPZ. The results suggest that YM-08050, a potent central dopaminergic blocker, is a potential antipsychotic drug with less extrapyramidal side effects than those of HPD and CPZ.
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PMID:Pharmacological and biochemical studies on a new potential neuroleptic, N-(1-benzyl-3-pyrrolidinyl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-08050). 4 18

Neuropharmacological properties of penfluridol (TLP-607) were investigated in experimental animals and were compared with those of haloperidol and chlorpromazine. Locomotor activity of mice significantly decreased at doses of 16-32 mg/kg p.o. Like haloperidol and chlorpromazine, TLP-607 (4-16 mg/kg p.o.) demonstrated catalepsy lasting for 48-72 hr in rats. TLP-607 strongly inhibited apomorphine-induced emesis in dogs and the ED50 was 0.016 mg/kg p.o. This effect lasted for 192 hr when administered 0.04 mg/kg p.o. TLP-607 antagnonized methamphetamine-induced stereotyped behavior in rats, and the ED50 was 1.83 ng/kg p.o. TLP-607 also inhibited conditioned avoidance responses in rats, and the ED50's in the pole climbing and Sidman avoidance methods were 6.73 and 3.4 mg/kg p.o., respectively. TLP-607 neither inhibited motor coordination nor enhanced hexobarbital-induced anesthesia in mice. These results suggest that TLP-607 is a potent and long-acting antipsychotic drug which has less neurotoxic side-effects.
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PMID:[Pharmacological studies of an antipschotic agent, penfluridol. (1). The central pharmacological actions]. 82 32

Butaclamol hydrochloride (AY-23,028) is a member of a new chemical class for which antipsychotic activity in humans has recently been demonstrated. The compound antagonized amphetamine-induced stereotyped behavior in rats, amphetamine toxicity in aggregated mice and apomorphine-induced emesis in dogs. It depressed both discriminated avoidance and continuous lever-pressing behavior in rats and inhibited ambulation and rearing in the open field. At higher doses, AY-23,028 induced catalepsy. Adrenergic blocking activity, measured by the antagonism of epinephrine-induced mortality, was weak. These pharmacological actions are characteristic of neuroleptic drugs. In the dose range where the aforementioned effects were observed AY-23,028 did not antagonize either the tetrabenazine-induced ptosis or the tremorine syndrome and did not cause either hypothermia or ataxia. The potency and onset of action of AY-23,028 were comparable to those of fluphenazine but AY-23,028 was of longer duration. The results are discussed in relation to current concepts of neuroleptic mechanisms.
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PMID:The behavioral pharmacology of butaclamol hydrochloride (AY-23,028), a new potent neuroleptic drug. 117 96

The potentiation of motor activity caused by ephedrine (Eph) in mice was inhibited by prazosin but not by sulpiride. This potentiation effect caused by apomorphine (Apo) was not inhibited by prazosin. Apo produced stereotyped behavior (including sniffing, licking, and biting) in rodents, but Eph was ineffective except at the toxic dose (400 mg.kg-1 in mice, 200 mg.kg-1 in rats). Apo antagonized haloperidol-induced catalepsy in mice whereas Eph had no such effect. Severe vomiting was evoked by Apo in dogs, but not by Eph even when lethal dose (20 mg.kg-1) was used. Palpebral ptosis induced by prazosin was abolished by intracerebroventricular injection of Eph in mice, but not affected by Apo. The results suggest that the central stimulating action of Eph is mediated by alpha 1-adrenoceptors and not by dopamine receptors.
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PMID:[Comparison of central stimulating effects between ephedrine and apomorphine]. 181 6

A series of 3-phenyl-2-piperazinyl-5H-1-benzazepines and related compounds were synthesized and evaluated for potential neuroleptic activity. The preparation of these compounds was carried out by 2,3-dichlorination of 3-phenyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-ones with phosphorus pentachloride followed by amination and concurrent dehydrochlorination. Compounds having the 4-chloro or 4-fluoro substituent in the 3-phenyl group were found to possess the neuroleptic-like activity. Among them, 2-(4-methyl-1-piperazinyl)-3-(4-fluorophenyl)-5H-1-benzazepine dihydrochloride (23) was comparable to chlorpromazine in inhibiting exploratory activity, conditioned avoidance response, and self-stimulation response and more potent than chlorpromazine in antagonizing apomorphine-induced emesis. These neuroleptic effects may be based on an antidopaminergic property of the compound. In causing catalepsy or ptosis, however, 23 was weaker than chlorpromazine. Therefore, this ring system is of interest as a novel class of neuroleptics. Some compounds having the 7-chloro or 7-bromo substituent showed potent anticonvulsant effects against maximal seizures induced by electroshock or pentylenetetrazole.
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PMID:A novel class of potential central nervous system agents. 3-Phenyl-2-(1-piperazinyl)-5H-1-benzazepines. 289 53

SCH39166 [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl- 5H-benzo[d]naptho-(2,1-b)azepine] is a benzonaphthazepine that has been evaluated as a selective D1 dopamine receptor antagonist. In vitro, SCH39166 (Ki = 3.6 nM) inhibited the binding of [3H]SCH23390 (a D1 specific compound) and blocked dopamine-stimulated adenylate cyclase (Ki = 9.1 nM); in contrast the Ki for SCH39166 to displace [3H]spiperone (D2) was greater than 1 microM and its Ki vs. [3H]-ketanserin (5-hydroxytryptamine2) binding was greater than 300 nM. In vivo, SCH39166 inhibited both rat and squirrel monkey conditioned avoidance responding (minimal effective dose = 10 and 1.78 mg/kg p.o., respectively) and had a duration of at least 6 hr in both species. In addition, SCH39166 antagonized apomorphine-induced stereotypy in rats (minimal effective dose = 10 mg/kg p.o.). These in vivo actions of SCH39166 are similar to the activity of typical dopamine antagonists. However, in contrast to D2-selective antagonists, SCH39166 failed to increase plasma prolactin levels, did not block apomorphine-induced emesis in the dog and had minimal effects on the striatal levels of homovanillic acid or dihydroxyphenylacetic acid. Furthermore, although immobility was seen after p.o. administration of SCH39166 using the inclined screen test, the drug did not cause catalepsy at doses up to 10 times its minimal effective dose in the rat conditioned avoidance response test. Additionally, SCH39166 inhibited apomorphine-induced climbing at lower doses than it inhibited apomorphine-induced sniffing in mice. The results from these latter two tests suggest that SCH39166 may have a reduced liability to produce extrapyramidal side effects. Therefore, based on this profile of activity, SCH39166 is a selective D1 dopamine receptor antagonist both in vitro and in vivo. Additionally, because this compound is longer acting in the primate than previously available D1 antagonists, it has potential utility as a clinically useful drug.
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PMID:Pharmacological profile of SCH39166: a dopamine D1 selective benzonaphthazepine with potential antipsychotic activity. 290 2

BMY-25801, 4-amino-5-chloro-N-[2-(diethylamino)ethyl]2-(1-methyl-2-oxopropoxy ) benzamide, a new antiemetic agent free of D2-dopamine receptor antagonist properties, was effective against emesis induced by cytostatic agents (cisplatin, cyclophosphamide and doxorubicin) and total body radiation in the ferret. It also was effective against cisplatin-induced emesis in the dog; however, it was inactive against emesis caused by apomorphine and hydergine in the same species. In terms of activity profile, BMY-25801 could be differentiated both from metoclopramide and domperidone. Metoclopramide was nonselectively active against emesis induced by cytostatic agents, radiation and D2-dopamine receptor agonists, whereas domperidone was selectively effective against emesis induced by apomorphine and hydergine only. BMY-25801 failed to reveal any D2-dopamine receptor antagonist properties in several pharmacological tests (catalepsy, apomorphine stereotypy, serum prolactin, striatal dihydroxyphenylacetic acid and [3H]spiperone displacement) whereas metoclopramide was uniformly active in these tests. The activity profile of domperidone was compatible with its classification as a peripherally acting D2-dopamine receptor antagonist. BMY-25801 and metoclopramide antagonized serotonin-induced bradycardia (Bezold-Jarisch reflex) in the anesthetized rat, a response involving peripheral neuronal 5-HT3 receptors. Thus, BMY-25801 represents a novel antiemetic acting independently of D2-dopamine receptor mechanisms; however, its exact mode of action remains unknown.
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PMID:BMY-25801, an antiemetic agent free of D2-dopamine receptor antagonist properties. 297 41

The substituted benzamide derivatives, dazopride and metoclopramide, enhanced field stimulation-induced contractions of guinea-pig stomach strips and gastric emptying in the guinea-pig after peripheral, intracerebroventricular and intrahypothalamic injection. In the isolated vagal nerve preparation from the rabbit, both compounds were shown to be 5-hydroxytryptamine M-receptor antagonists. Dazopride and metoclopramide were equipotent in antagonising cisplatin-induced emesis in the ferret, whereas metoclopramide was approximately 200 times more potent than dazopride in antagonising the emesis caused by the dopamine agonist 2-di-n-propylamino-5,6-dihydroxytetralin in the marmoset. In behavioural tests which indicate dopamine receptor antagonism in the rat, metoclopramide induced catalepsy, antagonised amphetamine-induced stereotypy and the hyperactivity induced by the intrastriatal injection of dopamine, caused body asymmetry on unilateral injection into the striatum and also antagonised apomorphine-induced climbing and circling behaviour in the mouse. In contrast, dazopride had little or no action in these tests and failed to displace [3H]spiperone in radioligand binding assays. The use of dazopride provides evidence to dissociate a dopamine receptor blockade from an ability to facilitate gastric emptying and to antagonise cisplatin-emesis, and indicates that antagonism of 5-hydroxytryptamine M-receptors is the essential basis of action for dazopride and plays an important role in the actions of metoclopramide.
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PMID:The action of dazopride to enhance gastric emptying and block emesis. 311 64

The emetic and catalepsy-inducing actions of buflomedil were studied in dog and mice. Oral administration of buflomedil (10-30 mg/kg) dose-dependently induced vomiting in dogs. On the other hand, the buflomedil-induced vomiting was inhibited by the pretreatment with domperidone (1 mg/kg, p.o.). A high dose of buflomedil (120-360 mg/kg, p.o.) induced catalepsy in mice, while a low dose of this agent (30-120 mg/kg, p.o.) had no enhancing effect on haloperidol-induced catalepsy. It was also found that the buflomedil-induced catalepsy was inhibited by the pretreatments with L-DOPA (300 mg/kg, i.p.) and bromocriptine (5 mg/kg, i.p.), respectively. These results suggest that buflomedil may induce emetic action as a dopamine agonist at a low dose, whereas it acts as a dopamine antagonist and a catalepsy inducer at a high concentration.
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PMID:[Emetic and catalepsy-inducing actions of buflomedil]. 325 Sep 15


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