title: Behavioral pharmacology of sigma-ligands.
abstract: Sigma (sigma) receptors, first defined as a subclass of opioid receptors, later confounded with the high affinity phencyclidine (PCP) binding sites, now are regarded as unique binding sites, distinct from opiate and PCP receptors, and related to higher brain function. The investigation of functional significance of sigma receptors in the brain has been hampered for many years by relative lack of specific tool drugs and by the unavailability of their coherent classification into postulated agonists and antagonists. However, a potential involvement of sigma receptors in psychotic disorders was first suggested soon after their discovery. The sigma receptors are classified into two subtypes, sigma (1) and sigma (2) receptors, of which the first was recently cloned from rodent and human tissues while the second has not yet been fully characterized. Although the precise mechanism of the functional response of these receptors is still uncertain, it is accepted that sigma receptors can modulate a number of central neurotransmitter systems, including noradrenergic, glutamatergic and dopaminergic ones. The sigma receptors have been postulated to be involved in numerous pharmacological and physiological functions, including motor disorders, psychotic disorders, neuroprotective mechanisms. In the last years, a number of compounds with a high affinity and selectivity for sigma binding sites have been discovered and investigated for their therapeutic potential. In this review, we try to summarize the behavioral effects of sigma receptor ligands that have been described, and their activity in animal models related to some brain disorders, especially schizophrenia and affective disorders.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland. skuza@if-pan.krakow.pl
authors.forename: G
authors.initials: G
authors.lastname: Skuza
authors.forename: K
authors.initials: K
authors.lastname: Wedzony
mesh_terms: D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D002934:Cinnamates / Q000493:pharmacokinetics; D019970:Cocaine-Related Disorders / Q000188:drug therapy; D003521:Cyclopropanes / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004347:Drug Interactions; D006801:Humans; D020902:Hypericum; D008024:Ligands; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011600:Psychopharmacology; D011618:Psychotic Disorders / Q000188:drug therapy; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use; D017480:Receptors, sigma / Q000819:agonists / Q000145:classification / Q000378:metabolism*; D013256:Steroids / Q000627:therapeutic use
chemical_list: C404207:1-(3-(4-(3-chlorophenyl)-1-piperazinyl)propyl)-3,4-dihydro-5-methoxy-2(1H)-quinolinone; D000928:Antidepressive Agents; D002934:Cinnamates; D003521:Cyclopropanes; D008024:Ligands; D018697:Nootropic Agents; D010879:Piperazines; D010936:Plant Extracts; D015363:Quinolones; D017480:Receptors, sigma; D013256:Steroids; C101789:SA 4503; C065310:igmesine