HT2 Receptor Agonist Challenge

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m-Chlorophenylpiperazine (mCPP) is an increasingly widely used 5-HT challenge which increases body temperature, stimulates PRL and ACTH/cortisol secretion and causes anxiety with GH stimulation occurring after intravenous but not oral administration.61,62 It is non-selective in its binding to 5-HT receptors,63,64 but animal studies suggest that many of its agonist effects are mediated by 5-HT2C receptors.65 mCPP's postsynaptic site of action has been challenged in animals by an in vivo microdialysis finding that it releases 5-HT and that the 5-HT reuptake inhibitor, fluoxetine, blocks this effect and partially attenuates mCPP-mediated PRL release.66 There are however contradictory reports about mCPP's affinity for the human brain 5-HT transporter,64,67 possibly related to different methodologies. In humans, the PRL, cortisol and anxiety responses are antagonized by non-selective 5-HT antagonists68,69 and by ritanserin70 as well as clozapine,71,72 but not by the 5-HT3 antagonist, endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3yl)-2,3-dihydro-3,3-dimethyl-indole-1-carboxamide HCl (BRL 46470)73 However, ondansetron is reported to attenuate cortisol and behavioral responses without affecting the PRL response in another study74 raising the possibility that 5-HT3 receptors may be involved in some responses. GH stimulation is not blocked by ritanserin70 raising doubts about the role of 5-HT2 receptors in this response. In summary the situation with regard to mCPP-mediated responses is complex with the strongest evidence linking PRL, cortisol and behavioral responses with 5HT2 receptors. Animal evidence further suggests that it is the 5-HT2C receptor subtype that is involved. However the assumption that responses purely reflect postsynaptic receptor function must be treated with caution.

6-Chloro-2-(l-piperazinyl)pyrazine (MK-212) binds to a variety of 5-HT receptors including 5-HT2A, 5-HT2C and 5-HT1A receptors.63 Animal studies show dose-related stimulation of PRL and ACTH/cortisol with antagonism by 5-HT2A/2C, but not 5-HT1A receptor antagonists.75-77 It stimulates PRL and cortisol secretion after oral administration in humans75,78 with pindolol pretreatment partially antagonizing PRL but not cortisol responses.79 Overall therefore the evidence is supportive of 5-HT2A/2C mediation of cortisol stimulation in humans with less certainty about the PRL response (reminiscent of 5-HTP, see above).

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Getting to Know Anxiety

Getting to Know Anxiety

Stop Letting Anxiety Rule Your Life And Take Back The Control You Desire Right Now! You don't have to keep letting your anxiety disorder run your life. You can take back your inner power and change your life for the better starting today! In order to have control of a thing, you first must understand it. And that is what this handy little guide will help you do. Understand this illness for what it is. And, what it isn't.

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