Posted by JackD on December 28, 2004, at 19:11:29
In reply to Calcium Channel Blockers in Bipolar Disorder, posted by ed_uk on December 22, 2004, at 17:18:57
Here's something:
------<Modulation of calcium and potassium currents by lamotrigine.
Grunze H, von Wegerer J, Greene RW, Walden J.
Psychiatrische Klinik der Universitat, Munchen, Deutschland. grunze@psy.med.uni-muenchen.de
Actions of the new antiepileptic drug lamotrigine (LTG) were characterized using extracellular and whole cell patch clamp recordings from rat CA1 and CA3 pyramidal cells in vitro. The results suggest that LTG, beside its previously described effect on the fast sodium inward current, also modulates - presumably voltage-gated - calcium currents and the transient potassium outward current ID. These may be effective mechanisms to inhibit pathological excitation in epilepsy and may be of potential benefit in treating underlying cellular disturbances in bipolar disorder.
PMID: 9778600 [PubMed - indexed for MEDLINE]
-----<
Eh, this one's KINDA relevant
-----<Voltage-activated calcium channels: targets of antiepileptic drug therapy?
Stefani A, Spadoni F, Bernardi G.
IRCCS Ospedale S. Lucia and Clinica Neurologica, Universita di Tor Vergata, Rome, Italy.
Voltage-gated calcium currents play important roles in controlling neuronal excitability. They also contribute to the epileptogenic discharge, including seizure maintenance and propagation. In the past decade, selective calcium channel blockers have been synthesized, aiding in the analysis of calcium channel subtypes by patch-clamp recordings. It is still a matter of debate whether whether any of the currently available antiepileptic drugs (AEDs) inhibit these conductances as part of their mechanism of action. We tested oxcarbazepine, lamotrigine, and felbamate and found that they consistently inhibited voltage-activated calcium currents in cortical and striatal neurons at clinically relevant concentrations. Low micromolar concentrations of GP 47779 (the active metabolite of oxcarbazepine) and lamotrigine reduced calcium conductances involved in the regulation of transmitter release. In contrast, felbamate blocked nifedipine-sensitive conductances at concentrations significantly lower than those required to modify N-methyl-D-aspartate (NMDA) responses or sodium currents. Aside from contributing to AED efficacy, this mechanism of action may have profound implications for preventing fast-developing cellular damage related to ischemic and traumatic brain injuries. Moreover, the effects of AEDs on voltage-gated calcium signals may lead to new therapeutic strategies for the treatment of neurodegenerative disorders.
Publication Types:
* Review
* Review, Tutorial
PMID: 9579933 [PubMed - indexed for MEDLINE]------<
Regarding all of my rantings about pain, and I think I remember amitriptyline also being mentioned in several posts that I skimmed, I thought this one might be of interest to you guys as well. Just food for thought.
------<Anticonvulsants in central pain.
Finnerup NB, Gottrup H, Jensen TS.
Department of Neurology and Danish Pain Research Centre, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark. finnerup@akhphd.au.dk
Treatment of central neuropathic pain (CP) following lesions of the CNS is a great challenge to the clinician. Preclinical and clinical studies indicate that neuronal hyperexcitability in damaged areas of the central nervous system plays a major role in the development of CP. Anticonvulsants are thought to act by increasing gamma-aminobutyric acid-mediated inhibition, decreasing abnormal neuronal hyperexcitability by modulating sodium and calcium channels or by inhibiting excitatory amino acid actions. The resulting inhibition of excess neuronal activity is thought to be the basis for the use of anticonvulsants in epilepsy as well as neuropathic pain. Both first-generation anticonvulsant drugs (e.g., phenytoin, benzodiazepines, valproate and carbamazepine) and second-generation anticonvulsant drugs (e.g., lamotrigine, gabapentin and topiramate) are used in CP conditions. However, few randomised controlled trials on the treatment of this condition have been published. Present suggestions for anticonvulsant treatment of CP are lamotrigine as the first choice, followed by gabapentin or carbamazepine/oxcarbazepine. These compounds are considered as effective as the antidepressant amitriptyline.
Publication Types:
* Review
* Review, Tutorial
PMID: 12387687 [PubMed - indexed for MEDLINE]
poster:JackD
thread:433001
URL: http://www.dr-bob.org/babble/20041228/msgs/435182.html