Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    5-HT2C receptor-mediated phosphoinositide turnover and the stimulus effects ofm-chlorophenylpiperazine (1995)
    Springer
    Psychopharmacology 122 (1995), S. 237-243 
    Details
    ISSN: 1432-2072
    Keywords: m-Chlorophenylpiperazine (mCPP) ; Drug-induced stimulus control ; 5-HT2A ; 5-HT2C
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was designed to investigate the hypothesis that agonist interactions at 5-HT2C receptors mediate the discriminative stimulus properties ofm-chlorophenylpiperazine (mCPP). Three structural classes of compounds have been described to stimulate increases in phosphoinositide (PI) hydrolysis at the 5-HT2C receptor site: phenylpiperazines, phenylalkylamines, and indolamines. Four representative phenylpiperazines, mCPP, TFMPP, MK-212 and quipazine, one phenylalkylamine, (-)DOM, and one indolamine, LSD, were employed in the present study. The efficacies of these compounds were defined (1) in vitro, with respect to their abilities to stimulate increases in PI hydrolysis in the choroid plexus, and (2) in vivo with respect to their abilities to substitute for the mCPP discriminative stimulus. In vitro intrinsic activity at the 5-HT2C site was expressed as a fraction of the maximal PI hydrolysis response elicited by serotonin (5-HT). MK-212 (fractional efficacy=1.1) and (-)DOM (0.77) were full agonists, while mCPP (0.72), LSD (0.27), quipazine (0.24), and TFMPP (0.22) were partial agonists with respect to the stimulation of PI hydrolysis at the 5-HT2C receptor. In vivo, each of the phenylpiperazines fully substituted for the mCPP stimulus, while (-)DOM (75%), and LSD (67%) elicited only partial substitution. While compounds with agonist activity at the 5-HT2C receptor in vitro substitute for the mCPP stimulus in vivo, no clear relationship exists between in vitro intrinsic activity at the 5-HT2C receptor with respect to the stimulation of PI turnover and maximal substitution for the mCPP stimulus in vivo. The present data suggest that mCPP elicits a compound stimulus which is mediated by agonist interactions at the 5-HT2C receptor and possibly additional interactions with 5-HT2A, 5-HT3, and/or 5-HT1B receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246545
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs I: Antagonist correlation analysis (1995)
    Springer
    Psychopharmacology 121 (1995), S. 347-356 
    Details
    ISSN: 1432-2072
    Keywords: Serotonin (5-HT) ; Drug-induced stimulus control (DISC) ; 5-HT2A ; 5-HT2C ; Antagonist correlation analysis ; Lysergic acid diethylamide (LSD) ; 2,5-Dimethoxy-4-methylamphetamine (DOM)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Investigations conducted over the past 3 decades have demonstrated that serotonergic receptors, specifically the 5-HT2A and 5-HT2C subtypes, play an important role in the behavioral effects of hallucinogenic compounds. The present study was designed to determine the respective significance of these two receptors in the stimulus effects of LSD and (−)DOM in the rat. Specifically, the interactions of a series of serotonergic antagonists (risperidone, pirenpirone, metergoline, ketanserin, loxapine, LY53857, pizotyline, spiperone, cyproheptadine, mesulergine, promethazine, and thioridazine) with the LSD stimulus and the (−)DOM stimulus in LSD-trained subjects was defined. From these data, IC50 values were determined for the inhibition of the LSD-appropriate responding elicited by either 0.1 mg/kg LSD (15-min pretreatment time) or 0.4 mg/kg (−)DOM (75-min pretreatment). In addition, the affinities of these antagonists for 5-HT2A and 5-HT2C receptors were determined in radioligand competition studies. 5-HT2A affinity correlated significantly with IC50 values for the blockade of the LSD (r=+0.75,P〈0.05) and (−) DOM (r=+0.95,P〈0.001) stimuli in the LSD trained subjects. 5-HT2C affinity did not correlate significantly with either series of IC50 values. These data indicate that (1) the stimulus effects of LSD, and (2) the substitution of (−)DOM for the LSD stimulus are mediated by agonist activity at 5-HT2A receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246074
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Role of 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs II: reassessment of LSD false positives (1995)
    Springer
    Psychopharmacology 121 (1995), S. 357-363 
    Details
    ISSN: 1432-2072
    Keywords: Drug-induced stimulus control ; Hallucinogens ; 5-HT2A ; 5-HT2C ; LSD (lysergic acid diethylamide) ; DOM (2,5-dimethoxy-4-methylamphetamine)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the context of animal studies of hallucinogens, an LSD-false positive is defined as a drug known to be devoid of hallucinogenic activity in humans but which nonetheless fully mimics LSD in animals. Quipazine, MK-212, lisuride, and yohimbine have all been reported to be LSD false positives. The present study was designed to determine whether these compounds also substitute for the stimulus effects of the more pharmacologically selective hallucinogen (−)DOM (0.56 mg/kg, 75-min pretreatment time). The LSD and (−)DOM stimuli fully generalized to quipazine (3.0 mg/kg) and lisuride (0.2 mg/kg), but only partially generalized to MK-212 (0.1–1.0 mg/kg) and yohimbine (2–20 mg/kg). In combination tests, pirenpirone (0.08 mg/kg), a compound with both D2 and 5-HT2A affinity, blocked the substitution of quipazine and lisuride for the (−)DOM stimulus. Ketanserin (2.5 mg/kg), an antagonist with greater than 1 order of magnitude higher affinity for 5-HT2A receptors than either 5-HT2C or D2 receptors, also fully blocked the substitution of these compounds for the (−)DOM stimulus, while the selective D2 antagonist thiothixene (0.1–1.0 mg/kg) failed to block the substitution of lisuride for the (−)DOM stimulus. These results suggest that quipazine and lisuride substitute for the stimulus properties of the phenylalkglamine hallucinogen (−)DOM via agonist activity at 5-HT2A receptors. In addition, these results suggest that 5-HT2A agonist activity may be required, but is not in itself sufficient, for indolamine and phenylalkglamine compounds to elicit hallucinations in humans. Finally, it is concluded that MK-212 and yohimbine are neither LSD nor (−)DOM false positives.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246075
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs III: the mechanistic basis for supersensitivity to the LSD stimulus following serotonin depletion (1995)
    Springer
    Psychopharmacology 121 (1995), S. 364-372 
    Details
    ISSN: 1432-2072
    Keywords: Serotonin ; Hallucinogens ; LSD ; p-Chloroamphetamine (PCA) ; p-Chlorophenylalanine (PCPA) ; Drug-induced stimulus control ; Phosphoinositide hydrolysis ; 5-HT2A ; 5-HT2C
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was designed to determine the effects ofp-chlorophenylalanine (PCPA) andp-chloroamphetamine (PCA) administration on (1) the levels of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in rat brain, (2) the sensitivity of LSD-trained rats to the stimulus effects of LSD, and (3) the maximal levels of 5-HT2A and 5-HT2C receptor mediated phosphoinositide (PI) hydrolysis in rat brain. PCA and PCPA both produced a significant depletion of whole brain 5-HT and 5-HIAA concentrations. The depletion of serotonin with PCPA, but not PCA, resulted in supersensitivity of LSD-trained subjects to the stimulus effects of LSD. Neither PCPA nor PCA treatment altered the maximal level of 5-HT2A receptor-mediated PI hydrolysis. However, PCPA, but not PCA, treatment resulted in a significant upregulation (46%,P〈0.05) of the maximal level of 5-HT2C receptor mediated PI hydrolysis. These data suggest that upregulation of the 5-HT2C receptor mediates the supersensitivity to LSD discriminative stimulus which follows the depletion of central nervous system serotonin by PCPA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246076
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects ofm-chlorophenylpiperazine (1995)
    Springer
    Psychopharmacology 119 (1995), S. 222-230 
    Details
    ISSN: 1432-2072
    Keywords: m-Chlorophenylpiperazine (mCPP) ; Serotonin (5-HT) ; Drug-induced stimulus control ; 5-HT2A ; 5-HT2C ; Antagonist correlation analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract m-Chlorophenylpiperazine (mCPP), a major metabolite of the atypical antidepressant trazadone, has been observed to produce marked physiological and behavioral effects in both humans and animals. These effects have been attributed to the interaction of mCPP with serotonergic receptors. The present study was designed to characterize those interactions of mCPP with central serotonergic receptors which mediate mCPP-induced stimulus control. A series of serotonergic antagonists (mesulergine, pizotyline, ketanserin, spiperone, risperidone, ritanserin, metergoline, pirenpirone, and LY53857) was tested for the ability to block the mCPP stimulus. The affinity of these antagonists for 5-HT2A and 5-HT2C receptors was then correlated with maximal percent inhibition of the mCPP stimulus. Kd at the 5-HT2C receptor was inversely proportional (r=−0.75,P〈0.05), and Kd at the 5-HT2A receptor directly proportional (r=+0.67,P〈0.05) to the maximal percent inhibition of the mCPP stimulus. The 5-HT2C selectivity ratio [Kd(5-HT2A)/Kd(5-HT2C)] of the antagonists was directly proportional (r=+0.86,P〈0.01) to maximal percent inhibition of the mCPP stimulus. A multiple regressions analysis indicated that 81% of the variance in the ability of a given antagonist to block the mCPP stimulus could be predicted on the basis of its affinity for 5-HT2A and 5-HT2C receptors. It is concluded that the stimulus effects of mCPP are mediated predominantly by a combination of agonist activity at 5-HT2C receptors and antagonist activity at 5-HT2A receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246164
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...