P-4-14 Pharmacology of the potential antipsychotic EMD 57445 in animals and humans

Bartoszyk, Gerd D.; Bender, H.; Heusener, A.; Schnorr, Carlos Eduardo

doi:10.1016/0924-977x(95)90534-k

Cited by 2 publications

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“…5) and apomorphine-induced stereotyped behaviors in rats ( Fig. 6) following oral, subcutaneous (3,4) and intraperitoneal (i.p.) administration (29).…”

Section: Behaviormentioning

confidence: 99%

“…Side effects in humans were studied in a double-blind, placebo-controlled, randomised clinical trial with 39 healthy male volunteers (3). Side effects were classified using the WHO Adverse Reaction Dictionary, Ciba-Geigy Version.…”

Section: Clinical Phase I Studiesmentioning

confidence: 99%

“…Safety and tolerability of a dose of 10 mg of EMD 57445 administered once daily for 7 consecutive days were studied in 12 male volunteers (3). Adverse events (10/12 subjects) were the same as reported in the single administration study.…”

Section: Clinical Phase I Studiesmentioning

confidence: 99%

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EMD 57445: A Selective Sigma Receptor Ligand with the Profile of an Atypical Neuroleptic

Bartoszyk

Bender²,

Hellmann

et al. 1996

CNS Drug Reviews

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Key Words: Atypical Neuroleptic-Clozapine-Dopamineantagonist-EMD 57445-Haloperidol-Panamesine-Schizophrenia-Sigma ligand.According to the classic dopamine (DA) hypothesis of schizophrenia, neuroleptic drugs must bind to the DA D, receptor. In addition several neuroleptic drugs, including the typical neuroleptic haloperidol and the atypical neuroleptic clozapine, exhibit high affinity to other receptors (13.26). Haloperidol particularly exhibits its highest affinity to the sigma site (25), which is distinct from the classical opiate or phencyclidine sites. Functional connections between sigma receptors and dopaminergic neurons in mesolimbic and cortical areas have been identified (5,7,14,19,41,43), and the involvement of sigma sites in the action of antipsychotic drugs has been shown in animal experiments (5,24,28). Further evidence for the significance of sigma sites in schizophrenia comes from investigations that benzomorphans cause symptoms that resemble schizophrenia in humans (20). Finally, several post-mortem studies have shown that the number of sigma binding sites in cortical and cerebellar regions is reduced in schizophrenic patients (37,38,44). Some attempts have been made to develop novel antipsychotic drugs with selective affinity for the sigma receptor (9,16,17,22,33,39) that would not have the extrapyramidal side effects (EPS) common to classic neuroleptics (25). Among these drugs rimcazole (17.18) initially has been shown to have some efficacy in humans (8,ll). Such drugs do, however, have EPS potential, and selective sigma ligands have ultimately not shown convincing antipsychotic efficacy in clinical trials (26). Drugs with greater selectivity (for sigma receptor subtypes) or drugs with higher intrinsic activity still must be developed (12,15,42). EMD 57445 was selected from a series of compounds that bear few structural

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“…5) and apomorphine-induced stereotyped behaviors in rats ( Fig. 6) following oral, subcutaneous (3,4) and intraperitoneal (i.p.) administration (29).…”

Section: Behaviormentioning

confidence: 99%

Section: Clinical Phase I Studiesmentioning

confidence: 99%