Pharmacology and neurochemistry of nefazodone, a novel antidepressant drug.
Nefazodone is a new antidepressant drug with a pharmacologic profile distinct from that of the tricyclic, monoamine oxidase inhibitor, and serotonin selective reuptake inhibitor antidepressants. Nefazodone was initially discovered for its ability to block 5-HT2A receptors and its reduced potency as an alpha 1-adrenergic blocker. It was later shown to inhibit both serotonin and norepinephrine uptake in vitro, attributes which most likely impart its clinical efficacy and which differentiate nefazodone from its chemical predecessor trazodone. The combination of these two mechanisms may ultimately result in a facilitation of 5-HT1A-mediated neurotransmission, which may be beneficial for treating symptoms of depression as evidenced by recent clinical findings. In addition, the preclinical profile of nefazodone demonstrates that it has decreased anticholinergic and antihistaminic activity relative to traditional agents. Clinical findings to date are consistent with these observations.
Taylor
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DP
Department of Neuropharmacology, Bristol-Myers Squibb Company, Wallingford, CT 06492-7600, USA.
Carter
R B
RB
Eison
A S
AS
Mullins
U L
UL
Smith
H L
HL
Torrente
J R
JR
Wright
R N
RN
Yocca
F D
FD
D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D003866:Depressive Disorder / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D009619:Nociceptors / Q000187:drug effects; D010879:Piperazines; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D000928:Antidepressive Agents; D010879:Piperazines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D014230:Triazoles; C051752:nefazodone