> A long list of what it doesn't do
A hypothalamic orexinergic/histaminergic pathway is involved in the pharmacology of modafinil.
I would say that this study helps to elucidate what modafinil does do. I am not sure how important dopamine reuptake inhibition is at clinically relevant concentrations. It is rather low in potency at the DAT.
- Scott
------------------------------------------------
Neurosci Lett. 2010 Oct 15;483(3):193-6. Epub 2010 Aug 7.
Modanifil activates the histaminergic system through the orexinergic neurons.
Ishizuka T, Murotani T, Yamatodani A.
Source
Department of Medical Science and Technology, Graduate School of Allied Health Sciences, Faculty of Medicine, Osaka University, Japan. ishizuka@cc.osaka-dent.ac.jp
Abstract
Modafinil is a drug used to treat hypersomnolence of narcolepsy. We previously reported that modafinil increases hypothalamic histamine release in rats but did not increase locomotor activity in histamine-depleted mice, suggesting that modafinil-induced locomotor activity involves the histaminergic system. Modafinil is also thought to express its effect through the orexinergic neurons, and orexin increases hypothalamic histamine release. These findings led us to investigate whether modafinil activates the histaminergic system via the orexinergic system. In the present study, we performed in vivo microdialysis and c-Fos immunohistochemistry to investigate whether the orexinergic system mediates the activation of the histaminergic system by modafinil using orexin neuron-deficient mice. Two hours after the injection, modafinil (150 mg/kg) caused a significant increase of histamine release compared to the basal release in wild type mice. However, modafinil had no effect on the histamine release in orexin neuron-deficient mice. By immunohistochemical study, we found that there was no neuronal activation in the tuberomammillary nucleus where the cell bodies of the histaminergic neurons exclusively exist in orexin neuron-deficient mice. These findings indicate that modafinil-induced increment of histamine release requires intact orexinergic neurons.
![[collapse]](http://www.dr-bob.org/images/babble/hide.gif)
this signature | Show by default | Change to hide (next time)Some see things as they are and ask why.
I dream of things that never were and ask why not.
- George Bernard Shaw