Profenamine, also known as Ethopropazine, is an antidyskinetic phenothiazine used to treat symptoms of Parkinson's disease. The drug improves muscle control and reuces stiffness which permits more normal movements of the body. It is also used to control severe reactions to certain medicines such as reserpine, phenothiazines, chlorprothixene, thiothixene, loxapine, and haloperidol. Because of its anticholinergic action, it is largely devoid of neurotoxic side effects. Profenamine partially blocks central cholinergic receptors, which helps to balance cholinergic and dopaminergic activity in the basal ganglia. This may decrease salivation and lead to smooth muscle relaxation. Profenamine causes a local anaesthetic effect due to the inhibition of NMDA glutamate receptors on nociceptive neuron pathways, which decreases pain. The inhibition of NMDA receptors causes hyperpolarization of the neuron, which prevents depolarizati0on. The excessive release of glutamate and hyperactivation on the dorsal horn neurons of the spinal cord is thought to be an integral feature of neuropathic pain, therefore the inhibition of this significantly decreases pain. Profenamine also inhibits muscarinic acetylcholine receptors M1 on the same neuron. Muscarinic acetylcholine receptors M1 normally would activate the Gq signalling cascade, which causes calcium to be released from the endoplasmic reticulum. This would then lead to depolarization. The inhibition of the muscarinic acetylcholine receptor M1 therefore causes further hyperpolarization of the neuron and prevents depolarization.

Profenamine Pathway References