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

A sixteen-week study examined the effect of Madopa and Sinemet on patients with Parkinson disease disease suffering nausea or vomiting as side-effects of levodopa therapy and compared the efficacy of the three preparations in controlling the symptoms of Parkinson disease. Following a control period on levodopa, 20 patients underwent four consecutive four-week regimens as follows: (1) double-blind, in which a randomized half received levodopa and half received Madopa; (2) single-blind, in which all received Madopa; (3) double-blind, in which a re-randomized half received Madopa and half Sinemet; and (4) single-blind, in which all received Sinemet. Levodopa administration via Sinemet and Madopa was held to a fixed 20% of prior levodopa dosage. Almost all patients showed great reduction in nausea and vomiting with both Madopa and Sinemet. Seventy percent of the patients showed improvement in disability compared to their levodopa baseline levels. Group means showed no difference between the improvement seen on Madopa and that seen on Sinemet. However, examination of individual responses showed that the majority of patients fared distinctly better on either Sinemet or Madopa.
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PMID:A double-blind comparison of levodopa, Madopa, and Sinemet in Parkinson disease. 35 36

The actions of the serotonin precursor 5-hydroxytryptophan (5-HTP), the agonist 5-methoxy-N,N-dimetyltryptamine (MeODMT) and quipazine (QPZ) and the antagonists cyproheptadine, methysergide and metergoline, were studied in the rat and in the common marmoset (Callithrix jacchus). The precursor and agonists elicited head shakes, forepaw padding, splayed hindlimbs, tremor and Straub tail in the rat. However, head shakes were not observed after MeODMT and Straub tail was not observed after QPZ. Carbidopa plus 5-HTP potentiated only head shakes, while tranylcypromine (TCP) plus 5-HTP potentiated all the behaviors above. In the marmoset, the action of these drugs elicited drowsiness, teeth chattering, ataxia, vomiting and decreased motor activity, although vomiting was not elicited by MeODMT and ataxia and drowsiness by QPZ. Although TCP plus 5-HTP potentiated all these behaviors, carbidopa plus 5-HTP was not effective. Rats treated with the antagonists (1.0, 5.0 and 10 mg/kg doses) did not show any of these behaviors, but marmosets treated with the same drugs developed "drowsiness", vomiting, and decreased motor activity; nonetheless, cyproheptadine (5.0 and 10 mg/kg doses) did not elicit "drowsiness", while increasing motor activity and the number of head shakes. Pretreatment of marmosets with these antagonists blocked only teeth chattering elicited by MeODMT (4.0 mg/kg) and QPZ (10 mg/kg). Pretreatment with haloperidol, p-chlorophenylalanine and alpha-methyl-P-tyrosine had no effect. The data obtained show that rats and marmosets present differential behavioral responses to the 5-HT drugs used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rats and marmosets respond differently to serotonin agonists and antagonists. 311 2

Sinemet (a combination of levodopa with carbidopa, a dopa-decarboxylase inhibitor) has replaced levodopa for early treatment of parkinsonism. The blocking of the systemic uptake of dopamine has eliminated the previous complications of nausea, vomiting, and cardiac and respiratory arrhythmias; pyridoxine need not now be avoided. However, the earlier appearance of abnormal involuntary movements, hallucinations, occasional psychosis, and a dopa-resistant state limits treatment efficacy. In all-over experience the combination drug offers the best relief for rigidity and akinesia. It has improved the quality of life and reduced mortality by one half. The greatest benefits appear in the first 3 years; then complications set in. The relation of complications to dosage is now better understood, and the ratio of dopa-decarboxylase inhibitor to levodopa inhibitor to levodopa of 1:4 is better than the previous 1:10. Levodopa with or without dopa decarboxylase is not a cure for parkinsonism. Some agonist drugs (bromocryptine, lisuride) are showing promise in the testing stage. The evolving knowledge about neurotransmitters and peptide messengers offers hope for the growing number of patients with parkinsonism.
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PMID:Sinemet and the treatment of Parkinsonism. 701 95

Glial cell line-derived neurotrophic factor (GDNF) stimulates the nigrostriatal dopaminergic pathway and improves motor functions in animal models of parkinsonism. Sinemet is currently the most widely used drug for treating Parkinson's disease. The present study has evaluated GDNF-Sinemet interactions in parkinsonian rhesus monkeys. Both GDNF and Sinemet, when given alone, significantly improved total parkinsonian scores. The response to Sinemet did not change after intracerebroventricular vehicle injections. In contrast, there was a functional interaction between GDNF and levodopa. When comparing the levodopa dose response before and after GDNF treatment, significant behavioral improvements were seen after trophic factor administration at every levodopa dose level except 500 mg. Adverse responses to Sinemet treatment alone in parkinsonian animals included vomiting, dykinesias, dystonias, and stereotypic movements. Combined GDNF-Sinemet treatment significantly reduced the occurrence of these levodopa-induced side effects, with a >90% decrease in adverse responses seen at the mid-Sinemet (250 mg levodopa-25 mg carbidopa) dose level. The only side effect from GDNF treatment was a transitory weight loss. Thus, combined GDNF-Sinemet treatment could be of therapeutic value in treating parkinsonism, by producing a greater functional response and by mitigating adverse responses to Sinemet treatment.
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PMID:Glial cell line-derived neurotrophic factor-levodopa interactions and reduction of side effects in parkinsonian monkeys. 926 31

Delta-9-tetrahydrocannabinol (delta-9-THC) prevents cisplatin-induced emesis via cannabinoid CB(1) receptors. Whether central and/or peripheral cannabinoid CB(1) receptors account for the antiemetic action(s) of delta-9-THC remains to be investigated. The 5-hydroxytryptamine (5-HT=serotonin) precursor, 5-hydroxytryptophan (5-HTP), is an indirect 5-HT agonist and simultaneously produces the head-twitch response (a centrally mediated serotonin 5-HT(2A) receptor-induced behavior) and emesis (a serotonin 5-HT(3) receptor-induced response, mediated by both peripheral and central mechanisms) in the least shrew (Cryptotis parva). The peripheral amino acid decarboxylase inhibitor, carbidopa, prevents the conversion of 5-HTP to 5-HT in the periphery and elevates 5-HTP levels in the central nervous system (CNS). When administered i.p. alone, a 50 mg/kg dose of 5-HTP failed to induce either behaviour while its 100 mg/kg dose produced robust frequencies of both head-twitch response and emesis. Pretreatment with carbidopa (0, 10, 20 and 40 mg/kg) potentiated the ability of both doses of 5-HTP to produce the head-twitch response in a dose-dependent but bell-shaped manner, with maximal potentiation occurring at 20 mg/kg carbidopa. Carbidopa dose-dependently reduced the frequency of 5-HTP (100 mg/kg)-induced emesis, whereas the 10 mg/kg dose potentiated, and the 20 and 40 mg/kg doses suppressed the frequency of vomits produced by the 50 mg/kg dose of 5-HTP. The peripheral and/or central antiemetic action(s) of delta-9-THC (0, 1, 2.5, 5, 10 and 20 mg/kg) against 5-HTP (100 mg/kg)-induced head-twitch response and emesis were investigated in different groups of carbidopa (0, 10 and 20 mg/kg) pretreated shrews. Irrespective of carbidopa treatment, delta-9-THC attenuated the frequency of 5-HTP-induced head-twitch response in a dose-dependent manner with similar ID(50) values. Although delta-9-THC also reduced the frequency of 5-HTP-induced emesis with similar ID(50s), at the 5 mg/kg delta-9-THC dose however, 5-HTP induced significantly less vomits in the 10 and 20 mg/kg carbidopa-treated groups relative to its 0 mg/kg control group. Moreover, increasing doses of carbidopa significantly shifted the inhibitory dose-response effect of delta-9-THC in protecting shrews from 5-HTP-induced emesis to the left. Relatively, a large dose of delta-9-THC (20 mg/kg) was required to significantly reduce the number of vomits produced by direct acting serotonergic 5-HT(3) receptor agonists, serotonin and 2-methylserotonin. Low doses of delta-9-THC (0.1-1 mg/kg) nearly completely prevented 2-methylserotonin-induced, centrally mediated, head-twitch and ear-scratch responses. The results indicate that delta-9-THC probably acts pre- and postsynaptically to attenuate emesis produced by indirect and direct acting 5-HT(3) receptor agonists via both central and peripheral mechanisms. In addition, delta-9-THC prevents 5-HTP-induced head-twitch and emesis via cannabinoid CB(1) receptors since the CB(1) receptor antagonist, SR 141716A [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide], countered the inhibitory actions of an effective dose of delta-9-THC against both behaviours.
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PMID:Central and peripheral mechanisms contribute to the antiemetic actions of delta-9-tetrahydrocannabinol against 5-hydroxytryptophan-induced emesis. 1504 52