Effect of Meta-Chlorophenylpiperazine (mCPP), A Central Serotonin Agonist and Vascular Serotonin Receptor Antagonist, on Blood Pressure in SHR

Abstract

mCPP (meta-chlorophenylpiperazine) has agonist activity at some central serotonin receptors and antagonist activity at peripheral vascular 5HT₂ receptors, both effects that have been postulated to lower blood pressure. mCPP (10 and 30 mg/kg, i.p. 1 hr after administration) increased serotonin and decreased 5-hydroxy-indolacetic acid (5-HIAA) brain concentrations and elevated serum corticosterone and prolactin, indications of central serotonergic agonist activities. The same doses of mCPP also antagonized vascular 5HT₂ receptors as measured by blockade of pressor responses to serotonin in pithed rats. Although mCPP could be demonstrated to activate central serotonergic receptors and block peripheral vascular 5HT₂ receptors, mCPP (10 and 30 mg/kg, i.p.) produced little effect on blood pressure in either the anesthetized or conscious spontaneously hypertensive rat (SHR) up to 1 hr after intraperitoneal administration. The findings are consistent with initial studies in normotensive humans that have not demonstrated a reduction in blood pressure clinically after mCPP in doses that produce elevations in serum cortisol and prolactin levels.

Key Words:

• Phenylpiperazines
• Serotonin Vascular Responses
• Blood Pressure in SHR
• Central Serotonin Agonist
• Vascular Serotonin Receptor Antagonist
• mChlorophenylpiperazine