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)

A series of new substituted benzamides has been synthesized and evaluated for dopamine antagonist activity and for antagonism of cisplatin-induced emesis in the dog and in the ferret. It was found that modification of the 2-methoxy substituent of metoclopramide was detrimental to dopaminergic D2 antagonism but not necessarily to antagonism of cisplatin-induced emesis. A number of analogues having a beta-keto, beta-hydroxy, beta-methoxy, beta-imino, or beta-unsaturated alkyloxy substituent instead of methoxy have shown equal or superior protection from emesis to that of metoclopramide. At the same time these compounds were found to be free of dopaminergic D2 antagonism in both in vitro ([3H]spiperone binding) and in vivo tests (rat catalepsy, antagonism of apomorphine-induced stereotypy in the rat, and apomorphine-induced emesis in the dog).
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PMID:Substituted benzamides. 1. Potential nondopaminergic antagonists of chemotherapy-induced nausea and emesis. 339 92

A new neuroleptic drug, Timiperone, is able to exert an antiapomorphine effect at doses smaller than cataleptogenic doses. Nineteen patients with urologic malignancy undergoing chemotherapy with cisplatin in combination with other agents were studied for the antiemetic efficacy of Timiperone. Six of 8 patients over 46 years old treated with Timiperone 6 mg/day p.o. from the day before undergoing DDP therapy to the last day of the therapy had no episode of vomiting and 2 patients had a few episodes of emesis (one and two episodes during 5 days of undergoing DDP, respectively). Five patients under 45 years old given Timiperone 6 mg/day by the same method had few episodes of vomiting, but suffered from extrapyramidal symptoms. Finally 6 patients undergoing DDP with Timiperone in combination with trihexyphenidyl suffered no symptoms of catalepsy but sometimes had mild vomiting episodes (1-4 times a day). We would like to propose that in antiemetic therapy with Timiperone for cisplatin-induced nausea and vomiting, a dose of 4.5 mg/day be given from two days before undergoing chemotherapy because of the cumulative effect of Timiperone.
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PMID:[Antiemetic therapy with timiperone in cisplatin-induced vomiting]. 375 27

The substituted benzamide sulpiride is considered an "atypical" neuroleptic and antipsychotic in that its pharmacology and clinical effects differ significantly from "classical" dopamine antagonists such as the butyrophenones and phenothiazines. Sulpiride increases dopamine turnover, elevates prolactin release, inhibits emesis, and is an effective antipsychotic. Sulpiride does not affect other transmitters, requires sodium for binding, does not induce catalepsy in rats or strong sedation and extrapyramidal side effects in humans. Compared to the butyrophenone and phenothiazine neuroleptics sulpiride is chemically distinct because it lacks certain properties associated with other dopamine antagonists. Poor blood-brain barrier penetration and preferential receptor affinities in different brain regions are the most probable reasons for sulpiride's effects in vivo. Nevertheless, the atypical conformation of sulpiride merits study of its structure-activity relationships. Experimental determination of specific pharmacophores could provide the data necessary for a computer analysis of structure. Comparison of relative orientation of sulpiride's pharmacophores with similar data on classical neuroleptics is suggested for study of structural requirements for dopamine antagonism.
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PMID:Sulpiride: assessment of a pharmacologically and chemically distinct neuroleptic. 614 15

In pharmacological screening amisulpride produces no catalepsy, no inhibition of stereotypic movements, yet a blockade of drug-induced vomiting. During an open clinical trial lasting 4 weeks, 14 patients (13 schizophrenics) were treated with the compound. The (BPRS-) syndromes anxiety/depression, thought disorder, activity, hostility and the global score showed significant improvement. With the AMDP system significant changes were seen in the paranoid-hallucinatory, manic, depressive and hostility syndromes as well as in the global score. No changes were revealed in anergia (BPRS) and apathia (AMDP). In the EEG a significant decrease in the frequency of alpha-rhythms was found. The scores of the Simpson-scale for extrapyramidal side effects were low, but there was an acute dystonic reaction in one patient. In three cases akathisia occurred; biperiden administration was necessary three times. In conclusion, amisulpride showed good antipsychotic efficacy without sedation. Contrary to expectations based on the pharmacological screening, we did find extrapyramidal side effects.
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PMID:Amisulpride--an open clinical study of a new benzamide in schizophrenic patients. 614 65

Two subtypes of cannabinoid receptors have been identified to date, the CB1 receptor, essentially located in the CNS, but also in peripheral tissues, and the CB2 receptor, found only at the periphery. The identification of delta9-tetrahydrocannabinol (delta9-THC) as the major active component of marijuana (Cannabis sativa), the recent emergence of potent synthetic ligands and the identification of anandamide and sn-2 arachidonylglycerol as putative endogenous ligands for cannabinoid receptors in the brain, have contributed to advancing cannabinoid pharmacology and approaching the neurobiological mechanisms involved in physiological and behavioral effects of cannabinoids. Most of the agonists exhibit nonselective affinity for CB1/CB2 receptors, and delta9-THC and anandamide probably act as partial agonists. Some recently synthesized molecules are highly selective for CB2 receptors, whereas selective agonists for the CB1 receptors are not yet available. A small number of antagonists exist that display a high selectivity for either CB1 or CB2 receptors. Cannabinomimetics produce complex pharmacological and behavioral effects that probably involve numerous neuronal substrates. Interactions with dopamine, acetylcholine, opiate, and GABAergic systems have been demonstrated in several brain structures. In animals, cannabinoid agonists such as delta9-THC, WIN 55,212-2, and CP 55,940 produce a characteristic combination of four symptoms, hypothermia, analgesia, hypoactivity, and catalepsy. They are reversed by the selective CB1 receptor antagonist, SR 141716, providing good evidence for the involvement of CB1-related mechanisms. Anandamide exhibits several differences, compared with other agonists. In particular, hypothermia, analgesia, and catalepsy induced by this endogenous ligand are not reversed by SR 141716. Cannabinoid-related processes seem also involved in cognition, memory, anxiety, control of appetite, emesis, inflammatory, and immune responses. Agonists may induce biphasic effects, for example, hyperactivity at low doses and severe motor deficits at larger doses. Intriguingly, although cannabis is widely used as recreational drug in humans, only a few studies revealed an appetitive potential of cannabimimetics in animals, and evidence for aversive effects of delta9-THC, WIN 55,212-2, and CP 55,940 is more readily obtained in a variety of tests. The selective blockade of CB1 receptors by SR 141716 impaired the perception of the appetitive value of positive reinforcers (food, cocaine, morphine) and reduced the motivation for sucrose, beer and alcohol consumption, indicating that positive incentive and/or motivational processes could be under a permissive control of CB1-related mechanisms. There is little evidence that cannabinoid systems are activated under basal conditions. However, by using SR 141716 as a tool, a tonic involvement of a CB1-mediated cannabinoid link has been demonstrated, notably in animals suffering from chronic pain, faced with anxiogenic stimuli or highly motivational reinforcers. Some effects of SR 141716 also suggest that CB1-related mechanisms exert a tonic control on cognitive processes. Extensive basic research is still needed to elucidate the roles of cannabinoid systems, both in the brain and at the periphery, in normal physiology and in diseases. Additional compounds, such as selective CB1 receptor agonists, ligands that do not cross the blood brain barrier, drugs interfering with synthesis, degradation or uptake of endogenous ligand(s) of CB receptors, are especially needed to understand when and how cannabinoid systems are activated. In turn, new therapeutic strategies would likely to emerge.
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PMID:Behavioral effects of cannabinoid agents in animals. 1080 37

Dopamine receptor antagonists are commonly used to counter the adverse effects of opioids such as hallucinations, delusions and emesis. However, most of these agents themselves have side effects, including extrapyramidal symptoms. Here, we investigated the effect of the dopamine system stabilizer aripiprazole on morphine-induced dopamine-related actions in mice. Morphine-induced hyperlocomotion and reward were significantly suppressed by either the dopamine receptor antagonist prochlorperazine or aripiprazole. Catalepsy was observed with a high dose of prochlorperazine, but not with an even higher dose of aripiprazole. The increased level of dialysate dopamine in the nucleus accumbens stimulated by morphine was significantly decreased by pretreatment with aripiprazole. These results suggest that the co-administration of aripiprazole may be useful for reducing the severity of morphine-induced dopamine-related side effects.
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PMID:Suppression of dopamine-related side effects of morphine by aripiprazole, a dopamine system stabilizer. 1895 42

From 2012 to 2014 in Japan, 214 cases of motor vehicle collisions were attributed to the use of illegal drugs. In 93 out of 96 investigated cases, the causative agents were a variety of synthetic cannabinoids (SCs). These SCs can be classified into three groups according to the lineage of the chemical structures: (1) naphthoyl indoles, such as MAM-2201, (2) quinolinyl ester indoles, such as 5F-PB-22, and (3) indazole carboxamides, such as 5F-AB-PINACA, 5F-AMB, and 5F-ADB. These SCs became available sequentially with increasing cannabinoid CB1 agonist potencies and reached a nationwide outbreak in the summer of 2014. They caused acute intoxication with impaired consciousness, anterograde amnesia (impaired memory), catalepsy with muscle rigidity, tachycardia, and vomiting or drooling soon after smoking. Drivers who had abused one of these SCs might unexpectedly experience the acute intoxication that caused uncontrolled driving. These SCs were generally difficult to detect from body fluid samples. It is thought that the highly lipophilic SCs disappear from the blood via rapid degradation by liver enzymes and selective accumulation into adipose tissues. Thus, much effort should be directed to the development of fast and sensitive chemical detection of the drug usage.
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PMID:Motor vehicle collisions caused by the 'super-strength' synthetic cannabinoids, MAM-2201, 5F-PB-22, 5F-AB-PINACA, 5F-AMB and 5F-ADB in Japan experienced from 2012 to 2014. 2870 66


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