Posted by JohnX2 on December 1, 2001, at 6:01:12
In reply to antihistamines and depression, posted by JohnX2 on December 1, 2001, at 5:51:11
Another abstract on antihistamine induced
nmda transmission:Antihistamine terfenadine potentiates NMDA receptor-mediated calcium influx, oxygen radical formation, and neuronal death.
Brain Res 2000 Oct 13;880(1-2):17-27 (ISSN: 0006-8993)Diaz-Trelles R; Novelli A; Vega JA; Marini A; Fernandez-Sanchez MT [Find other articles with these Authors]
Department of Biochemistry and Molecular Biology, School of Medicine, University of Oviedo, 33071, Oviedo, Spain.We previously reported that the histamine H1 receptor antagonist terfenadine enhances the excitotoxic response to N-methyl-D-aspartate (NMDA) receptor agonists in cerebellar neurons. Here
we investigated whether this unexpected action of terfenadine relates to its antihistamine activity, and which specific events in the signal cascade coupled to NMDA receptors are affected by
terfenadine. Low concentrations of NMDA (100 microM) or glutamate (15 microM) that were only slightly (< 20%) toxic when added alone, caused extensive cell death in cultures pre-exposed
to terfenadine (5 microM) for 5 h. Terfenadine potentiation of NMDA receptor response was mimicked by other H1 antagonists, including chlorpheniramine (25 microM), oxatomide (20
microM), and triprolidine (50 microM), was prevented by histamine (1 mM), and did not require RNA synthesis. Terfenadine increased NMDA-mediated intracellular calcium and cGMP
synthesis by approximately 2.4 and 4 fold respectively. NMDA receptor-induced cell death in terfenadine-treated neurons was associated with a massive production of hydrogen peroxides, and
was significantly inhibited by the application of either (+)-alpha-tocopherol (200 microM) or the endogenous antioxidant melatonin (200 microM) 15 min before or up to 30 min after receptor
stimulation. This operational time window suggests that an enduring production of reactive oxygen species is critical for terfenadine-induced NMDA receptor-mediated neurodegeneration, and
strengthens the importance of antioxidants for the treatment of excitotoxic injury. Our results also provide direct evidence for antihistamine drugs enhancing the transduction signaling activated by
NMDA receptors in cerebellar neurons.>
> This looks interesting.
> I get an unexplained sustained anti-depressant effect
> from the anti-histamine chlorpheniramine maleate.
> I found this abstract as well as others discussing
> the stimulant properties of h1 antagonists.
>
> -john
>
> Increased levels of extracellular dopamine in neostriatum and nucleus accumbens after histamine H1 receptor blockade.
>
>
> Naunyn Schmiedebergs Arch Pharmacol 1998 Oct;358(4):423-9 (ISSN: 0028-1298)
>
> Dringenberg HC; de Souza-Silva MA; Schwarting RK; Huston JP [Find other articles with these Authors]
> Department of Psychology, Queen's University, Kingston, Ontario, Canada.
>
> The dopaminergic system plays a central role in the processing of reward or reinforcement since drugs that have reinforcing properties all share the ability to elevate dopamine (DA) levels in the
> nucleus accumbens or neostriatum. Histamine H1 receptor antagonists are known to have reinforcing effects in humans and laboratory rats. Here, we examined the effect of systemic (i.p.)
> treatment with two H1 antagonists, chlorpheniramine and pyrilamine, on the extracellular levels of DA and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in
> the neostriatum and nucleus accumbens of urethane-anesthetized rats. Dopamine and metabolites were measured using in vivo microdialysis and HPLC with electrochemical detection. Saline
> injections did not produce significant effects on DA, DOPAC, or HVA levels in the neostriatum or nucleus accumbens. In the neostriatum, chlorpheniramine administration (5 and 20 mg/kg)
> produced a sustained increase in DA to approximately 140 and 180% of pre-injection baseline levels, respectively. In the nucleus accumbens, chlorpheniramine (20 mg/kg) produced a transient
> increase in DA levels to about 300% of baseline. In both the neostriatum and nucleus accumbens, DOPAC and HVA decreased after chlorpheniramine treatment. Pyrilamine administration (10
> and 20 mg/kg) produced a sustained increase in neostriatal DA levels to 140 and 165%, respectively, and accumbens DA increased transiently to 230% after a dose of 20 mg/kg. Levels of
> neostriatal and accumbens DOPAC and HVA decreased after pyrilamine treatment. These results show that H1 antagonists can potently enhance DA levels in the neostriatum and nucleus
> accumbens of urethane-anesthetized rats. The neurochemical effects on DA and its metabolites seen here (increased DA, decreased DOPAC and HVA) are similar to those commonly observed
> with drugs of abuse (e.g. psychostimulants). The interaction of H1 antagonists with dopaminergic transmission may explain the reinforcing effects and abuse potential associated with these
> compounds.
>
>
poster:JohnX2
thread:85709
URL: http://www.dr-bob.org/babble/20011123/msgs/85710.html