A potential 5-HT1A receptor antagonist: p-MPPI

Kung, Hank F.; Kung, Mei Ping; Clarke, William P.; Maayani, Saul; Zhuang, Zhi Ping

doi:10.1016/0024-3205(94)00686-5

Cited by 62 publications

(25 citation statements)

References 11 publications

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“…The IC 50 values for both agonists were very similar to those reported in mammals (Middlemiss and Fozard, 1983;Beer et al, 1993). The effect of the 5-HT 1A agonist was blocked only by the 5-HT 1A antagonist p-MPPI (Kung et al, 1994), whereas the effect of L-694,247 was blocked only by the 5-HT 1D antagonist GR127935 (Skingle et al, 1993). Therefore, these receptors have a very similar pharmacology to the mammalian 5-HT 1A and 5-HT 1D receptors, and we propose that they are the amphibian equivalents of these receptors.…”

Section: Identity Of Serotonergic Receptorssupporting

confidence: 83%

“…The effects of 8-OH-DPAT (100 nM), a selective 5-HT 1A agonist (Middlemiss and Fozard, 1983), were fully blocked by the selective 5-HT 1A antagonist p-MPPI (100 nM; Kung et al, 1994) in six examined neurons ( Fig. 3A 2 ,B).…”

Section: -Ht Receptor Subtypes Involved In the Inhibition Of The Hvamentioning

confidence: 90%

“…Our results are consistent with an involvement of 5-HT 1A and 5-HT 1D receptors. In brief, the effects of 5-HT, 8-OH-DPAT, 5-C T, and ␣-methyl-5-HT were blocked by the 5-HT 1A antagonist p-M PPI (Kung et al, 1994) (Fig. 6, Table 1).…”

Section: -Ht Antagonistsmentioning

confidence: 91%

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Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

Sun

Dale

1997

J. Neurosci.

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The primary sensory Rohon-Beard (R-B) neurons of Xenopus larvae are highly analogous to the C fibers of the mammalian pain pathway. We explored the actions of 5-HT by studying the modulation of Ca 2ϩ currents. In ϳ80% of the acutely isolated R-B neurons, 5-HT inhibited the high voltage-activated (HVA) currents by 16% (n ϭ 29) and the T-type currents by 24% (n ϭ 41). The modulation of the T-type and the HVA currents was mimicked by selective 5-HT 1A and 5-HT 1D agonists: 8-OH-DPAT and L-694,247. The effects of the agonists were blocked by their respective 5-HT 1A or 5-HT 1D antagonists: p-MPPI and GR127935, suggesting that both 5-HT 1A and 5-HT 1D receptors were involved. Approximately 70% of the actions of 5-HT on HVA currents was occluded by -conotoxin-GVIA (N-type channel blocker), whereas the rest of the modulation (ϳ30%) was occluded by Ͻ100 nM -agatoxin-TK (P/Q-type channel blocker). This suggests that 5-HT acts on N-and P/Q-type Ca 2ϩ channels. Neither the modulation of the T-type nor that of the HVA currents was accompanied by changes in their voltage-dependent kinetics. Cell-attached patch-clamp recordings suggest that the modulation of the T-type channel occurs through a membrane-delimited second messenger. We have studied the functional consequences of the modulation of T-type Ca 2ϩ channels and have found that these channels play a role in spike initiation in R-B neurons. Modulation of T-type channels by 5-HT therefore could modulate the sensitivity of this sensory pathway by increasing the thresholds of R-B neurons. This is a new and potentially important locus for modulation of sensory pathways in vertebrates.

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Section: Identity Of Serotonergic Receptorssupporting

confidence: 83%

Section: -Ht Receptor Subtypes Involved In the Inhibition Of The Hvamentioning

confidence: 90%

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Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

Sun

Dale

1997

J. Neurosci.

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“…Such an experimental outcome would suggest that the affective aspects of drug withdrawal may be homologous to the core symptom of depression of "diminished interest or pleasure" in rewarding stimuli. It was also hypothesized that this serotonergic drug treatment would not reverse the somatic signs of nicotine withdrawal that most likely do not reflect affective aspects of withdrawal.The combination treatment of a SSRI together with the relatively selective 5-HT 1A receptor antagonist Kung et al 1994aKung et al , 1994bKung et al , 1995 was selected based on the following considerations. First, the threshold elevations associated with nicotine (Epping-Jordan et al 1998) and amphetamine (Lin et al 1999(Lin et al , 2000Paterson et al 2000) withdrawal, and the increases in somatic signs seen during nicotine withdrawal (Epping-Jordan et al 1998) are relatively short lasting phenomena (3-5 days) that do not allow the detection of the effects of pharmacological treatments that may require chronic administration for producing their effect.…”

mentioning

confidence: 99%

Fluoxetine Combined with a Serotonin-1A Receptor Antagonist Reversed Reward Deficits Observed during Nicotine and Amphetamine Withdrawal in Rats

Harrison

Liem

Markou

2001

Neuropsychopharmacology

158

126

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Cessation of chronic nicotine or amphetamine administration precipitates withdrawal syndromes characterized by affective symptoms, including "diminished interest or pleasure" in rewarding stimuli (i.e., anhedonia) (American Psychiatric Association 1994;Covey et al. 1998;Glassman 1993;Hughes 1992). Interestingly, the symptom of "diminished interest or pleasure" is not only a symptom of drug withdrawal, but also a core symptom of depression and a negative symptom of schizophrenia (American Psychiatric Association 1994;Markou et al. 1998). Brain reward threshold elevation is an operational measure of this symptom because it reflects diminished sensitivity to rewarding electrical stimuli. In rats, withdrawal from drugs of abuse belonging to diverse pharmacological classes, such as nicotine (Epping-Jordan et al. 1998 Watkins et al. 2000b), amphetamine Zacharko 1980a, 1980b;Kokkinidis et al. 1980Kokkinidis et al. , 1986 Barrett 1976, 1980;Lin et al. 1999Lin et al. , 2000Paterson et al. 2000;Wise and Munn 1995), cocaine (Baldo et al. 1999;Kokkinidis and McCarter 1990; Koob 1991, 1992a;Markou et al. 1992) morphine (Schulteis et al. 1994) and ethanol (Schulteis et al. 1995) elevated brain stimulation reward thresholds.In addition to the affective aspects of drug withdrawal reflected in threshold elevations, nicotine, opiate, or ethanol withdrawal also lead to alterations in a set of behaviors termed somatic signs. In the case of nicotine, these somatic signs are primarily gasps, writhes, eye blinks, and ptosis (Epping-Jordan et al. 1998;Hildebrand et al. 1997Hildebrand et al. , 1999Malin et al. 1992). It is unlikely that these somatic signs in the rat reflect the affective component of drug withdrawal. Nevertheless, the study of both threshold elevations and somatic signs permits the investigation of the effects of manipulations on the various aspects of withdrawal.Based on evidence demonstrating the efficacy of serotonergic antidepressant treatments, reduced cerebrospinal fluid levels of serotonin metabolites, endocrine measures reflecting reduced serotonergic neurotransmission and the exacerbation of depressive symptomatology seen after serotonin (5-HT) depletion in depressed individuals, it is hypothesized that reduced serotonergic neurotransmission underlies at least some aspects or some subtypes of non-drug-induced depressions (for reviews, see Caldecott-Hazard et al. 1991; CaldecottHazard and Schneider 1992;Heninger et al. 1996;Markou et al. 1998;Meltzer and Lowy 1988;Willner 1985). The purpose of the present study was to test the hypothesis that reduced serotonergic neurotransmission mediates some of the affective aspects, not only of non-drug-induced depressions, but also of druginduced depressions. Thus, the present study tested the hypothesis that enhancement of serotonergic neurotransmission through acute administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Wong et al. 1995) in combination with a relatively selective 5-HT 1A receptor antagonist would alleviate the symptom of "dimin...

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“…Among agonists with a particularly high degree of selectivity are 8- (11,12). Antagonists of a similar selectivity include 4-(2Ј-methoxyphenyl)-1-[2Ј-(n-2Љ-pyridinyl)-p-iodobenzamido]ethyl-piperazine (p-MPPI) and the related fluorobenzamido analogue (p-MPPF) (13)(14)(15)(16). The neuroleptic spiperone is also a commonly employed antagonist for the 5-HT 1A receptor, although it blocks a number of other receptors as well (17,18).…”

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confidence: 99%

Agonist-independent Activation of Gz by the 5-Hydroxytryptamine1A Receptor Co-expressed in Spodoptera frugiperda Cells

Barr¹,

Manning

1997

Journal of Biological Chemistry

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A potential 5-HT1A receptor antagonist: p-MPPI

Cited by 62 publications

References 11 publications

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

Fluoxetine Combined with a Serotonin-1A Receptor Antagonist Reversed Reward Deficits Observed during Nicotine and Amphetamine Withdrawal in Rats

Agonist-independent Activation of Gz by the 5-Hydroxytryptamine1A Receptor Co-expressed in Spodoptera frugiperda Cells

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A potential 5-HT1A receptor antagonist: p-MPPI

Cited by 62 publications

References 11 publications

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca2+Currents in the Primary Sensory Neurons ofXenopusLarvae

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca2+Currents in the Primary Sensory Neurons ofXenopusLarvae

Fluoxetine Combined with a Serotonin-1A Receptor Antagonist Reversed Reward Deficits Observed during Nicotine and Amphetamine Withdrawal in Rats

Agonist-independent Activation of Gz by the 5-Hydroxytryptamine1A Receptor Co-expressed in Spodoptera frugiperda Cells

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Product

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Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae