m-CPP hydrochloride

Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells.[Pubmed:10498829]

Br J Pharmacol. 1999 Sep;128(1):13-20.

1. The goal of this study was to characterize the agonist pharmacology of human 5-HT2A, 5-HT2B and 5-HT2C (VSV) receptors expressed in CHO-K1 (Chinese hamster ovary) cells. 2. We used a fluorometric imaging plate reader (FLIPR) which allows rapid detection of rises in intracellular calcium levels upon the addition of agonists. 3. Stimulation of all three receptors by 5-HT caused a robust concentration dependent increase in intracellular calcium levels. No such effect was observed from non-transfected control CHO-K1 cells. 4. The rank order of potency of agonists at the different receptor subtypes varied. Tryptamines, BW-723C86, d-norfenfluramine, Ro 60-0175 and LSD exhibited the following rank order of potency; 5-HT2B>5-HT2C>5-HT2A. Piperazines such as m-Chlorophenylpiperazine (mCPP), ORG-12962, MK-212 and also ORG-37684 exhibited a rank order of potency of 5-HT2C>5-HT2B>5-HT2A. The phenylisopropylamines DOI and DOB had a rank order of 5-HT2A>5-HT2B>5-HT2C. 5. Many agonists tested had partial agonist actions when compared to 5-HT, and a wide range of relative efficacies were exhibited, which was cell line dependent. For example, mCPP had a relative efficacy of 65% at 5-HT2C receptors but <25% at either 5-HT2A or 5-HT2B receptors. 6. Interpretation of literature values of functional assays using different cell lines, different receptor expression levels and different receptor isoforms, is complex. Species differences and the previous use of antagonist radioligands to characterize agonist potency in binding assays emphasizes the importance of studying agonists in the same experiment using the same assay conditions and parental cell lines.

International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin).[Pubmed:7938165]

Pharmacol Rev. 1994 Jun;46(2):157-203.

It is evident that in the last decade or so, a vast amount of new information has become available concerning the various 5-HT receptor types and their characteristics. This derives from two main research approaches, operational pharmacology, using selective ligands (both agonists and antagonists), and, more recently, molecular biology. Although the scientific community continues to deliberate about the hierarchy of criteria for neurotransmitter receptor characterisation, there seems good agreement between the two approaches regarding 5-HT receptor classification. In addition, the information regarding transduction mechanisms and second messengers is also entirely consistent. Thus, on the basis of these essential criteria for receptor characterisation and classification, there are at least three main groups or classes of 5-HT receptor: 5-HT1, 5-HT2, and 5-HT3. Each group is not only operationally but also structurally distinct, with each receptor group having its own distinct transducing system. The more recently identified 5-HT4 receptor almost undoubtedly represents a fourth 5-HT receptor class on the basis of operational and transductional data, but this will only be definitively shown when the cDNA for the receptor has been cloned and the amino acid sequence of the protein is known. Although those 5-HT receptors that have been fully characterised and classified to date (and, hence, named with confidence) would seem to mediate the majority of the actions of 5-HT throughout the mammalian body, not all receptors for 5-HT are fully encompassed within our scheme of classification. These apparent anomalies must be recognised and need further study. They may or may not represent new groups of 5-HT receptor or subtypes of already known groups of 5-HT receptor. Even though the cDNAs for the 5-ht1E, 5-ht1F, 5-ht5, 5-ht6, and 5-ht7 receptors have been cloned and their amino acid sequence defined, more data are necessary concerning their operational and transductional characteristics before one can be confident of the suitability of their appellations. Therefore, it is important to rationalise in concert all of the available data from studies involving both operational approaches of the classical pharmacological type and those from molecular and cellular biology.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of 1-(m-chlorophenyl)piperazine and 1-(m-trifluoromethylphenyl)piperazine on locomotor activity.[Pubmed:2709329]

J Pharmacol Exp Ther. 1989 Apr;249(1):155-64.

The piperazine-type 5-hydroxytryptamine (5-HT) agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP), 1-(m-chlorophenyl)-piperazine (m-CPP), 1-(p-chlorophenyl)piperazine (p-CPP) and MK-212 [6-chloro-2-(1-piperazinyl)pyrazine], produced a dose-dependent suppression of spontaneous ambulatory behavior in rats. Pretreatment with the 5-HT antagonists metergoline, methysergide or mianserin, but not selective 5-HT2 or catecholamine antagonists, blocked the reduction of activity caused by TFMPP suggesting that the stimulation of 5-HT receptors was involved in causing this behavioral effect. Other behavioral signs of 5-HT receptor stimulation, such as the 5-HT behavioral syndrome or head-shaking behavior, were not observed in rats injected with TFMPP, m-CPP or MK-212 except at toxic doses. The ability of piperazine agonists to reduce locomotor activity in rats was altered by long-term changes in 5-HT neurotransmission. The destruction of 5-HT neurons by i.v.t. injection of the neurotoxin 5,7-dihydroxytryptamine potentiated the ability of m-CPP to inhibit ambulatory behavior. On the other hand, elevating 5-HT content by administering the monoamine oxidase inhibitors phenelzine or nialamide for 7 days reduced the ability of m-CPP to suppress locomotor activity. Acute administration of the monoamine oxidase inhibitors, or chronic administration of other antidepressants such as desmethylimipramine or iprindole, failed to alter m-CPPs activity-suppressant effects. These studies suggest that chronic changes in 5-HT neurotransmission produce compensatory changes which alter the behavioral response to these piperazine agonists. Taken together with other evidence that both TFMPP and m-CPP are agonists at 5-HT1B and 5-HT1C receptors, the effects of TFMPP and m-CPP on locomotor activity may be associated with the selective activation of 5-HT1C, or possibly 5-HT1B, receptors.