2010
DOI: 10.1007/s00213-010-2005-6
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PPI deficit induced by amphetamine is attenuated by the histamine H1 antagonist pyrilamine, but is exacerbated by the serotonin 5-HT2 antagonist ketanserin

Abstract: Based on its ability to reverse amphetamine-induced PPI deficits, blockade of histamine H(1) receptors seems to contribute to the therapeutic effect of the antipsychotic clozapine. Serotonin 5-HT(2)-receptor blockade, though, does not appear to contribute to this effect, and may in fact detract from it.

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Cited by 9 publications
(6 citation statements)
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References 42 publications
(51 reference statements)
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“…The finding that an H 1 -receptor antagonist can enhance PPI in humans is consistent with results in the animal literature showing that pyrilamine (another H 1 -antagonist) antagonizes PPI deficits in rats caused by either amphetamine (Larrauri and Levin 2010) or dizocilpine (Roegge et al, 2007). In the first case, 20 mg/kg pyrilamine significantly increased PPI after it was disrupted by a 1 mg/kg dose of amphetamine, but a higher dose (40 mg/kg) only showed a non-significant trend toward an increase, and a lower dose (10 mg/kg) could not reverse the amphetamine-induced PPI disruption.…”
Section: Discussionsupporting
confidence: 89%
See 1 more Smart Citation
“…The finding that an H 1 -receptor antagonist can enhance PPI in humans is consistent with results in the animal literature showing that pyrilamine (another H 1 -antagonist) antagonizes PPI deficits in rats caused by either amphetamine (Larrauri and Levin 2010) or dizocilpine (Roegge et al, 2007). In the first case, 20 mg/kg pyrilamine significantly increased PPI after it was disrupted by a 1 mg/kg dose of amphetamine, but a higher dose (40 mg/kg) only showed a non-significant trend toward an increase, and a lower dose (10 mg/kg) could not reverse the amphetamine-induced PPI disruption.…”
Section: Discussionsupporting
confidence: 89%
“…In a related way, it has been previously reported that a moderate dose of the histamine H 1 -receptor antagonist pyrilamine can effectively antagonize the PPI deficits caused by the NMDA-receptor antagonist dizocilpine (Roegge et al, 2007) in rats. It has also been shown that the same dose range of pyrilamine can effectively reverse the PPI impairment in rats caused by amphetamine (Larrauri and Levin 2010). To date, these results have not been extended to humans with PPI deficits.…”
Section: Introductionmentioning
confidence: 99%
“…have contrasting effects on the startle reflex, with MK‐801 increasing the startle amplitude, while methamphetamine reduces the startle amplitude (Figures and ). These results are in agreement with previous reports on MK‐801 and amphetamine effect on startle response (Kinney et al ., ; Long et al ., ; Arai et al ., ; Egashira et al ., ; Larrauri and Levin, ). Thus, at these doses, it appears that potentiation of dopaminergic signalling and inhibition of glutamate signalling may have distinct effects on the neurocircuitry involved in startle response.…”
Section: Discussionmentioning
confidence: 99%
“…Another 5-HT 2A receptor antagonist ketanserin partially attenuated the hyperthermia induced by the same dose of 5-MeO-DMT (Figure 5I), suggesting that ketanserin might be less effective than MDL-100907 in antagonizing 5-HT 2A receptor-mediated pharmacological and toxicological effects. The difference in attenuation of 5-MeO-DMT-induced hyperthermia between MDL-100907 and ketanserin might be attributed to their differing pharmacodynamic profiles because ketanserin also binds to some other targets such as noradrenaline and histamine receptors and vesicular monoamine transporter-2 (Gopalakrishnan et al, 2007; Larrauri and Levin, 2010; Marin et al, 1990). In addition, both MDL-100907 and ketanserin attenuated harmaline-5-MeO-DMT-induced hyperthermia, and converted it to significant hypothermia (Figure 6), indicating 5-HT 2A receptor played a predominant role in harmaline-5-MeO-DMT-induced hyperthermic effect.…”
Section: Discussionmentioning
confidence: 99%