Novel agents affecting enkephalinergic and histaminergic transmissions in brain
Progress in cephalalgia therapy may be anticipated from the development of novel classes of drugs that affect either the transmission of pain messages or the control of vascular mechanisms in the brain. A valuable strategy for achieving such an aim consists in identifying new molecular targets that are critically involved in neurotransmitter metabolism or actions. This line has been followed in recent years in our laboratory to identify the mechanisms responsible for opioid peptide inactivation, and for the control of histamine release from its cerebral neurones. In both cases, relevant molecular targets were identified — that is, two ‘neuropeptidases’ responsible for enkephalin breakdown, and the H3 autoreceptor responsible for the control of histamine synthesis and release. Agents able to interact selectively and potently with these various targets have been rationally designed to help us to study the corresponding control mechanisms. These agents may constitute new drugs to be used in human therapeutics.
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