Disease relevance of MK-212

• Forty-eight hours after a single injection of mianserin, there was a shift to the right in the dose-response relationship for MK-212-induced hyperthermia [1].
• In contrast, pindolol (0.03-0.1 mg/kg) and methiothepin (10 mg/kg) selectively antagonized hypothermia induced by 8-OH-DPAT but did not alter hyperthermia induced by MK-212 [2].
• DOI (5-HT1C/2 agonist, 0-5 mg/kg i.p.) and 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) (less selective, but predominantly a 5-HT1C agonist, 0-20 mg/kg i.p.) were administered 18 hr after the final antidepressant injection and 30 min before decapitation [3].
• Our present study indicated the possible value of MK-212 and (-)-baclofen in the management of clinical myoclonus [4].
• Besides, MK 212 failed to influence catalepsy following administration of haloperidol [5].

Psychiatry related information on MK-212

• Prolactin and cortisol responses to MK-212, a serotonin agonist, in obsessive-compulsive disorder [6].
• In the second experiment, rats were exposed for 10 min in an open-field arena to further assess the interference of the same MK-212 doses upon locomotor activity [7].
• Central serotonergic modulation of drinking behavior induced by water deprivation: effect of a serotonergic agonist (MK-212) administered intracerebroventricularly [8].

High impact information on MK-212

• Finally, the Phe340-->Leu340 mutant receptors displayed an attenuated or abolished ability to augment phosphoinositide hydrolysis in COS-7 cells with four separate agonists (5-HT, MK-212, bufotenine, and quipazine) [9].
• Effect of the serotonin agonist, MK-212, on body temperature in schizophrenia [10].
• The effects of 6-chloro-2-(1-piperaziny)pyrazine (MK-212), a centrally acting 5-HT1C/5-HT2 agonist, on body temperature and behavior were assessed using a single-blind cross-over design in 23 schizophrenic patients and 22 normal controls [10].
• CGS 12066B (0.5-10.0 mg/kg) and MK-212 (0.3-10.0 mg/kg), selective agonists for 5-HT1B and 5-HT1C sites, respectively, failed to influence this particular form of adaptive pain inhibition [11].
• Thus, the microinjection of both SKF 81297 (R-(+)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide) and MK 212 (6-chloro-2-(1-piperazinyl)pyrazine hydrochloride), a D1 and 5-HT(2C) receptor agonist, respectively, blocked MDMA sensitization [12].

Chemical compound and disease context of MK-212

• To examine further the serotoninergic system in obsessive-compulsive disorder (OCD), the plasma concentrations of cortisol and prolactin and the behavioral responses after oral administration of MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine), a serotonin agonist, and placebo were studied in 17 patients with OCD and nine normal controls [6].
• Xylamidine, a peripheral 5-HT antagonist, had no significant effect on hyperthermia induced by MK-212 or hypothermia induced by 8-OH-DPAT.(ABSTRACT TRUNCATED AT 250 WORDS)[2]
• On the contrary, the 5-HT receptor agonists quipazine (3 mg/kg) and MK-212 (3 mg/kg), significantly blocked apomorphine hypothermia [13].
• In contrast, the chronic administration of 5-MeODMT did not alter the magnitude of hyperthermia or corticosterone secretion induced by the acute administration of MK-212 (1.0 mg/kg) [14].
• Three pharmacological tools namely zimelidine, danitracen and MK 212, were selected to examine the nature of involvement of serotonergic neurotransmission in catalepsy, an undesirable side effect following administration of neuroleptics in rats [5].

Biological context of MK-212

• The improved smooth pursuit performance after MK-212 was not related to side-effects [15].
• The effect of apomorphine, MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine) and placebo on smooth pursuit gain and corrective saccades in normal subjects [15].
• Furthermore, MK-212, 5-HT and 5-fluorotryptamine stimulate phosphoinositide turnover with potencies that resemble their potencies at the S2 but not the S1 binding site [16].
• It was found that in rats that were repeatedly treated with corticosterone the number of 2-chloro-6-(1-piperazinyl)pyrazine HCl (MK 212)-induced, 5-HT2C receptor-mediated penile erections were reduced, whereas both MK 212 and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced 5-HT2A receptor-mediated head shakes were increased [17].
• Food intake was reduced 54% by MK-212 (p < .001) [18].

Anatomical context of MK-212

• A variety of 5-HT2 or mixed 5-HT1/5-HT2 agonists stimulated total [3H]inositol phosphate formation in the immature rat cortex and hippocampus with a rank order of potency [alpha(+)-methyl-5-HT greater than quipazine greater than MK 212 greater than 5-HT] which resembles their potencies at the 5-HT2 binding site [19].
• 1. In in vivo experiments, DOI (a 5-HT(2) receptor agonist), MK-212 (a 5-HT(2C) receptor agonist), and BW-723C86 (a 5-HT(2B) receptor agonist) were applied by ionophoresis to neurones in the rat nucleus tractus solitarius (NTS) receiving vagal afferent input [20].
• SB 242084 (2. 5 mg/kg i.p.) antagonized also the decrease in DA release induced by mCPP and MK 212 in the nucleus accumbens [21].
• Quantitative morphometry of IL cells at the ultrastructural level revealed that MK-212 treatment selectively causes depletion of electron-lucent but not electron-dense secretory granules from the cytoplasm of IL cells [22].
• 5-HT, alpha-methyl-5-HT, quipazine, MK-212, mCPP (m-chlorophenylpiperazine) and TFMPP (m-trifluoromethylphenylpiperazine) are less potent and efficient in stimulating phosphoinositide turnover in the hippocampus and cerebral cortex than in the choroid plexus [23].

Associations of MK-212 with other chemical compounds

• The plasma PRL, but not the plasma cortisol response, following MK-212 was also significantly lower in the alcoholics [24].
• Pre-exposure with the 5-HT2C receptor agonist MK 212 [6-chloro-2(1-piperazinyl)pyrazine] partially prevented the fluvoxamine-induced CTA, pre-exposure with the 5-HT2A/2C receptor agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] did not prevent the CTA induced by fluvoxamine [25].
• The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5-HT agonists is difficult to explain [26].
• Ketanserin, a selective 5-HT2 antagonist, reversed the effects of MK-212 in some cases, but the patterning of responses remained disturbed.(ABSTRACT TRUNCATED AT 250 WORDS)[27]
• Fluoxetine and DMI potentiated the MK-212- and DOI-induced increase of plasma oxytocin levels and potentiated the effect of DOI on plasma adrenocorticotropic hormone (corticotropin) and prolactin levels [3].

Gene context of MK-212

• Chronic treatment with mianserin (10 mg/kg/day), a tetracyclic antidepressant with 5-HT1C and 5-HT2 receptor antagonistic properties, did not change PE induced by MK 212, but caused an increase of PE induced by DOI and a decrease of DOI-induced HS [28].
• METHODS: In the first experiment, male Wistar rats were exposed for 5 min to the EPM 27 min following intraperitoneal (i.p.) (1.0 ml/kg) injections of the preferential 5-HT2C receptor agonist 6-chloro-2[1-piperazinyl]pyrazine (MK-212) at doses of 1.0, 2.0, or 4.0 mg/kg [7].
• Clozapine administration to schizophrenic patients was found to produce dopamine2 (D-2) and serotonin2 (5-HT2) receptor blockade, as evidenced by the ability to block the increases in growth hormone and cortisol secretion produced by apomorphine and MK-212, respectively, direct acting dopamine (DA) and 5-HT2 agonists [29].
• In contrast, the effect of the high dose of MK-212 on plasma prolactin concentration was reduced by both antidepressants [3].
• The MK-212-induced increase in plasma concentrations of corticosterone and beta-END were not affected by treatment with the 5-HT1A antagonists spiperone and (-)-pindolol [30].

Analytical, diagnostic and therapeutic context of MK-212

• MK-212 was effective despite bilateral vagotomy [31].
• MK-212 was not self-administered by rats, while the self-administration of amphetamine and morphine were demonstrated using the same experimental protocol [32].
• Male Wistar rats implanted with a cannula in the 3rd ventricle were injected with the 5-HT1C/5-HT2 agonist 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) at doses of 0.5, 5, 25, 50 and 125 nmol/2 microliters [8].

References