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The Effect of Subchronic Dosing of Ciproxifan and Clobenpropit on Dopamine and Histamine Levels in Rats.

Mahmood D, Pillai KK, Khanam R, Jahan K, Goswami D, Akhtar M - J Exp Neurosci (2015)

Bottom Line: MK-801-induced increase of horizontal activity was reduced with CPX and CBP.Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP.In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK-801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi, India.

ABSTRACT
The present study was designed to investigate the effect of once daily for 7-day (subchronic treatment) dosing of histamine H3 receptor antagonists, ciproxifan (CPX) (3 mg/kg, i.p.), and clobenpropit (CBP) (15 mg/kg, i.p), including clozapine (CLZ) (3.0 mg/kg, i.p.) and chlorpromazine (CPZ) (3.0 mg/kg, i.p.), the atypical and typical antipsychotic, respectively, on MK-801(0.2 mg/kg, i.p.)-induced locomotor activity, and dopamine and histamine levels in rats. Dopamine and histamine levels were measured in striatum and hypothalamus, respectively, of rat brain. Atypical and typical antipsychotics were used to serve as clinically relevant reference agents to compare the effects of the H3 receptor antagonists. MK-801-induced increase of horizontal activity was reduced with CPX and CBP. The attenuation of MK-801-induced locomotor hyperactivity produced by CPX and CBP was comparable to CLZ and CPZ. MK-801 raised dopamine levels in the striatum, which was reduced in rats pretreated with CPX and CBP. CPZ also lowered striatal dopamine levels, though the decrease was less robust compared to CLZ, CPX and CBP. MK-801 increased histamine content although to a lesser degree. Subchronic treatment with CPX and CBP exhibited further increase in histamine levels in the hypothalamus compared to the MK-801 treatment alone. Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP. In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK-801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors.

No MeSH data available.


MS-MS-SCAN of histamine.
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Related In: Results  -  Collection


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f5-jen-9-2015-073: MS-MS-SCAN of histamine.

Mentions: Treatment with RAMH (10 mg/kg, i.p.), in the CPX+MK-801+RAMH or CBP+RAMH+MK-801 treatment group, tended to reverse (P<0.05) the increase of the histamine levels mediated by CPX or CBP administration in the CPX+MK-801 or CBP+MK-801 treatment group. The administration of CPX or CBP per se had no influence on either dopamine or histamine levels in the striatum and hypothalamus, respectively. The MS-MS scan of daughter ion of dopamine was recorded at m/z = 154 (Fig. 4). The MS-MS scan of daughter ion of histamine was recorded at m/z = 111 [M+ +H] (Fig. 5).


The Effect of Subchronic Dosing of Ciproxifan and Clobenpropit on Dopamine and Histamine Levels in Rats.

Mahmood D, Pillai KK, Khanam R, Jahan K, Goswami D, Akhtar M - J Exp Neurosci (2015)

MS-MS-SCAN of histamine.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4556212&req=5

f5-jen-9-2015-073: MS-MS-SCAN of histamine.
Mentions: Treatment with RAMH (10 mg/kg, i.p.), in the CPX+MK-801+RAMH or CBP+RAMH+MK-801 treatment group, tended to reverse (P<0.05) the increase of the histamine levels mediated by CPX or CBP administration in the CPX+MK-801 or CBP+MK-801 treatment group. The administration of CPX or CBP per se had no influence on either dopamine or histamine levels in the striatum and hypothalamus, respectively. The MS-MS scan of daughter ion of dopamine was recorded at m/z = 154 (Fig. 4). The MS-MS scan of daughter ion of histamine was recorded at m/z = 111 [M+ +H] (Fig. 5).

Bottom Line: MK-801-induced increase of horizontal activity was reduced with CPX and CBP.Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP.In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK-801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi, India.

ABSTRACT
The present study was designed to investigate the effect of once daily for 7-day (subchronic treatment) dosing of histamine H3 receptor antagonists, ciproxifan (CPX) (3 mg/kg, i.p.), and clobenpropit (CBP) (15 mg/kg, i.p), including clozapine (CLZ) (3.0 mg/kg, i.p.) and chlorpromazine (CPZ) (3.0 mg/kg, i.p.), the atypical and typical antipsychotic, respectively, on MK-801(0.2 mg/kg, i.p.)-induced locomotor activity, and dopamine and histamine levels in rats. Dopamine and histamine levels were measured in striatum and hypothalamus, respectively, of rat brain. Atypical and typical antipsychotics were used to serve as clinically relevant reference agents to compare the effects of the H3 receptor antagonists. MK-801-induced increase of horizontal activity was reduced with CPX and CBP. The attenuation of MK-801-induced locomotor hyperactivity produced by CPX and CBP was comparable to CLZ and CPZ. MK-801 raised dopamine levels in the striatum, which was reduced in rats pretreated with CPX and CBP. CPZ also lowered striatal dopamine levels, though the decrease was less robust compared to CLZ, CPX and CBP. MK-801 increased histamine content although to a lesser degree. Subchronic treatment with CPX and CBP exhibited further increase in histamine levels in the hypothalamus compared to the MK-801 treatment alone. Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP. In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK-801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors.

No MeSH data available.