ok smarty pants... what about 4AP? I've always wonder about that drug during trials. Anyone know? (just kidding Todd) Best Wishes In a message dated 9/25/2009 7:17:16 P.M. Central Daylight Time, [email protected] writes:
Just wanted to pass along a forum post...I am trying Tizanidine for the first time. Let me add another perspective from the viewpoint of mechanisms. When you mix drugs, it is useful to know the mechanisms by which the drugs act, whether they are pushing the same buttons or different buttons on the neurons. Baclofen is what is called a GABA-B receptor agonist. In other words, it turns on GABA-B receptors. GABA and glycine are the two major inhibitory neurotransmitters of the central nervous system. GABA plays a more important role in motor systems and particularly in the spinal cord. GABA presses two buttons (receptors) on neurons: the GABA-A and GABA-B receptors. GABA-A turns on chloride channels that makes the membrane more negative and reduces the excitability of neurons. GABA-B turns on intracellular messengers that tell the neurons to activate cellular programs that reduce their excitability. Diazepam is a GABA receptor enhancer. In other words, it enhances the effects of GABA. It is called a tranquilizer because it calms people down by reducing neuronal excitability. It is also a "muscle relaxant" because it reduces the excitability of spinal reflexes. The problem is that diazepam has effects on the brain. Two of its most important side effects are short-term memory loss and sleepiness. It is also addictive in the sense that the brain becomes dependent on it and sudden withdrawal of the drug may result in unpleasant hyperexcitability states. Tizanidine is an alpha-2 adrenergic receptor agonist. It reduces excitatory amino acid release by spinal interneurons. It also seems to have an anti-nociceptive (anti-pain) and anti-convulsant (anti-seizure) activity. It has relatively mild or transient cardiovascular side-effects. While high doses may depress the central nervous system, there is sufficient separation of its CNS depressive effects and its anti-spasticity activity so that this is not usually a problem. Its main side effects are dry mouth, flushing, tiredness, and weakness. Dantrolene is a muscle relaxant that acts directly on the excitation-contraction coupling in muscle cells, through the ryanodine receptor. It is the specific and high effective treatment of a condition called malignant hyperthermia (which results from overactivity of muscle) and neuroleptic malignant syndrome (which also causes overactivity of muscle) that may occur with a variety of drug (or anesthesia) overdose and intoxication. Before baclofen, dantolene was the most popular anti-spasticity drug. Today, it is rarely prescribed alone for spasticity because its main side-effect is muscle weakness. Dantrolene should not be used in people who have pre-existing liver disease, compromised lung function, severe cardiovascular impairment, or weak muscles whose function is crucial for activity of daily living. Thus, when you take diazepam along with baclofen, both drugs press the same GABA button, enhancing each other's side-effects. Tizanidine acts on a different mechanism, directly affecting spasticity by reducing glutamate neurotransmitter release and excitability of spinal circuits. Dantrolene reduces spasticity by inhibiting muscle, which is not desirable particularly in people cervical spinal cord injury with compromised lung function and weak hand muscles but it might be useful for people with paraplegia for whom baclofen plus tizanidine are insufficient to control spasticity. Todd C6
