The proposed role of neurotransmitter receptors in the pathophysiology of human myoclonic disorders.
The hypothesis that central neurotransmitter receptor abnormalities are the basis of human myoclonic disorders is novel. Receptor abnormalities in any of several different neurotransmitter systems implicated in myoclonus may be genetic or the consequence of various brain injuries. These abnormalities might define pharmacologic subgroups of possible relevance to the clinical, neurophysiologic, and pathologic heterogeneity of myoclonus. Receptor abnormalities may be the primary pathophysiologic defect, involving the surface recognition site or effector-transducer mechanisms in the defect, involving the surface recognition site or effector-transducer mechanisms in the post-synaptic cell. Alternatively, changes in receptor density or affinity may be adaptive (recovery of function) or maladaptive (supersensitivity, subsensitivity, dysregulation). Drug treatments, then, could be targeted at the receptor changes, reversing abnormalities and enhancing compensatory mechanisms. Current therapy may inadvertently have such an effect. Polytherapy may be justified to target more than one component of the "pharmacologic receptor". Identification of receptor abnormalities in human post-mortem brain may have diagnostic and therapeutic significance. New advances in the pharmacologic selectivity of receptor agonists and antagonists and in the measurement of receptors should be applied to the problem of myoclonus.
Pranzatelli
M R
MR
Department of Neurology, College of Physicians and Surgeons, Columbia University New York, New York 10032.
D006916:5-Hydroxytryptophan / Q000627:therapeutic use; D000818:Animals; D001696:Biomechanical Phenomena; D006801:Humans; D009207:Myoclonus / Q000188:drug therapy / Q000209:etiology*; D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000502:physiology
D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D012701:Serotonin; D006916:5-Hydroxytryptophan