Serotonin antagonism

Four principal mechanisms have been cited to explain the diverse physiological mechanisms of ginger. Broadly, these are (1) eicosanoid inhibition, (2) serotonin antagonism, (3) substance P release, and (4) Ca2-i-/ATPase activity. 

Serotonin is also involved in opioid effects on the transmission and processing of nociceptive information at a level rostral to the PAG. Borszcz (1999) and Borszcz and Streltsov (2000) have demonstrated that the antinociceptive effect of morphine administered into the PAG can be attenuated be serotonin antagonism in the central nucleus of the amygdala and the parafascicular nucleus of the thalamus, suggesting that serotonin is also involved in pain processing in higher brain centers. 

Ceulemans DL, Gelders YG, Hoppenbrouwers ML, Reyntjens AJ, Janssen PA. Effect of serotonin antagonism in schizophrenia a pilot study with setoperone. Psychopharmacology (Berl) 1985 85 329-332. 

Methylation at the indole nitrogen group specifically enhances the serotonin antagonism exhibited by all ergot alkaloids. For example, 1-methyl-LSD and l-methyl-2-bromo-LSD exhibit antiserotonin activity several times greater than that of their nonmethylated parent compounds. 

Nichols, D.E Dyer, D.C. Lipophilicity and Serotonin Antagonism Activity in a Series of 4-substituted Mescaline Analogues. J Med Chem, 20 259-301,1977. 

Cerletti, A. Doepfner, W. Comparative Study on the Serotonin Antagonism of Amide Derivatives of Lysergic Acid and of Ergot Alkaloids J. Pharmacol Exp. Then (1958) 122 124-136... 

Ziprasidone is an atypical antipsychotic in clinical use for both schizophrenia and bipolar disorder (see footnote 1). It has a high affinity for dopamine, serotonin, and alpha-adrenergic receptors and a moderate affinity for histamine receptors. The exact mechanism of action of ziprasidone is unknown. However it has been presumed that its antipsychotic activity is mediated primarily by antagonism at dopamine receptors, specifically D2. Serotonin antagonism may also play a role in the effectiveness of ziprasidone. Antagonism at histaminic and alpha adrenergic receptors are likely responsible for some of the side effects of ziprasidone, such as sedation and orthostasis. The worldwide sales of ziprasidone are expected to be 1 billion in 2009. 

Future Outlook for Antidepressants. Third-generation antidepressants are expected to combine superior efficacy and improved safety, but are unlikely to reduce the onset of therapeutic action in depressed patients (179). Many dmgs in clinical development as antidepressive agents focus on estabhshed properties such as inhibition of serotonin, dopamine, and/or noradrenaline reuptake, agonistic or antagonistic action at various serotonin receptor subtypes, presynaptic tt2-adrenoceptor antagonism, or specific monoamine—oxidase type A inhibition. Examples include buspirone (3) (only... 

QUESTION Have you made any attempt to antagonize the MBDB stimulus with serotonin antagonists ... 

The neurotoxic effects of all these compounds are antagonized by inhibitors of monoamine uptake (table 1), implicating the membrane uptake carrier on serotonin and dopamine neurons in the mechanism of neurotoxicity. In this regard, these amphetamines are like a drug somewhat related in structure, namely l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP), a Parkinsonism-causing neurotoxic dmg that has been studied intensely since 1983 (Langston and Irwin 1986). In the case of MPTP, the mechanism by which inhibitors of the dopamine uptake carrier block the neurotoxicity toward dopamine neurons (mainly nigrostriatal dopamine neurons) seems clear. A metabolite of MPTP, l-methyl-4-phenylpyridinium (MPP-I-), has been shown to be a substrate for the dopamine uptake carrier (Javitch et al. 1985). Thus accumulation of MPP-I-, formed metabolically from... 

Rimonabant (382) was also included in a clinical study to assess the safety and efficacy of four novel compounds for the treatment of schizophrenia and psychoaffective disorder [378]. The other compounds included in the trial were a neurokinin NK3 antagonist, a serotonin 2A/2C antagonist and a neurotensin NTSl antagonist. Halopeiidol and placebo groups were used as controls in the study. Sixty-nine patients received (382) (20 mg once per day), which failed to demonstrate efficacy in this trial. The reasons for the lack of efficacy may be due to inadequate dosing or an indication that CBi antagonism is not appropriate in the treatment of this condition. 

Cyproheptadine Antagonizes serotonin 20-32 mg/day Sedation, increased Efficacy variable. 

The answer is b. (Katzung, pp 504-505.) Amoxapine is a heterocyclic antidepressant that has effects on norepinephrine and serotonin uptake. It is useful in psychotic patients who are depressed. The dopaminergic antagonism caused by amoxapine may lead to the amenorrhea-galactorrhea syndrome. 

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