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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by ben on May 22, 2005, at 2:12:28
Read this:
Trazodone and its active metabolite m-chlorophenylpiperazine as partial agonists at 5-HT1A receptors assessed by [35S]GTP{gamma}S binding.Odagaki Y, Toyoshima R, Yamauchi T.
Department of Psychiatry, Saitama Medical School, Moroyama-machi, Iruma-gun, Saitama, Japan.
Trazodone is an effective antidepressant drug with a broad therapeutic spectrum, including anxiolytic efficacy. Although trazodone is usually referred to as a serotonin (5-HT) reuptake inhibitor, this pharmacological effect appears to be too weak to fully account for its clinical effectiveness. The present study aimed to elucidate the agonist properties of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP), at 5-HT(1A) receptors by means of the guanosine-5'-O-(3-[(35)S]thio)-triphosphate ([(35)S]GTPgammaS) binding assay. In membranes prepared from Chinese hamster ovary cells expressing human 5-HT(1A) receptors (CHO/h5-HT(1A)), trazodone behaved as an almost full agonist and m-CPP was also a highly efficacious partial agonist at 5-HT(1A) receptors. The intrinsic activities of both compounds were higher than those of tandospirone and buspirone, which are clinically effective anxiolytics with well-known 5-HT(1A) partial agonist properties. These effects were replicated in the 5-HT(1A) receptor-mediated [(35)S]GTPgamma(S) binding assay in native rat brain membranes (at least in hippocampal membranes), although the intrinsic activities of the compounds were low and differently ranked compared to those in CHO/h5-HT(1A) cell membranes. When considering the implications of 5-HT(1A) receptors in anxiety and/or depression, as well as the clinical effectiveness of azapirone anxiolytics with partial 5-HT(1A) receptor agonist properties such as buspirone, it is possible that the agonist effects on 5-HT(1A) receptors of trazodone and its active metabolite m-CPP presented in this study contribute, at least in part, to the clinical efficacy of the atypical antidepressant trazodone.
PMID: 15888508 [PubMed - in process]
Seems that trazodone is more a 5-HT-1 agonist than an serotonine reuptake inhibitor - similar to buspirone!
Posted by SLS on May 22, 2005, at 7:40:37
In reply to Trazodone = 5-HT-1 agonist (similar to buspirone), posted by ben on May 22, 2005, at 2:12:28
> Read this:
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15888508&query_hl=18
>
>
> Trazodone and its active metabolite m-chlorophenylpiperazine as partial agonists at 5-HT1A receptors assessed by [35S]GTP{gamma}S binding.
>
> Odagaki Y, Toyoshima R, Yamauchi T.
>
> Department of Psychiatry, Saitama Medical School, Moroyama-machi, Iruma-gun, Saitama, Japan.
>
> Trazodone is an effective antidepressant drug with a broad therapeutic spectrum, including anxiolytic efficacy. Although trazodone is usually referred to as a serotonin (5-HT) reuptake inhibitor, this pharmacological effect appears to be too weak to fully account for its clinical effectiveness. The present study aimed to elucidate the agonist properties of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP), at 5-HT(1A) receptors by means of the guanosine-5'-O-(3-[(35)S]thio)-triphosphate ([(35)S]GTPgammaS) binding assay. In membranes prepared from Chinese hamster ovary cells expressing human 5-HT(1A) receptors (CHO/h5-HT(1A)), trazodone behaved as an almost full agonist and m-CPP was also a highly efficacious partial agonist at 5-HT(1A) receptors. The intrinsic activities of both compounds were higher than those of tandospirone and buspirone, which are clinically effective anxiolytics with well-known 5-HT(1A) partial agonist properties. These effects were replicated in the 5-HT(1A) receptor-mediated [(35)S]GTPgamma(S) binding assay in native rat brain membranes (at least in hippocampal membranes), although the intrinsic activities of the compounds were low and differently ranked compared to those in CHO/h5-HT(1A) cell membranes. When considering the implications of 5-HT(1A) receptors in anxiety and/or depression, as well as the clinical effectiveness of azapirone anxiolytics with partial 5-HT(1A) receptor agonist properties such as buspirone, it is possible that the agonist effects on 5-HT(1A) receptors of trazodone and its active metabolite m-CPP presented in this study contribute, at least in part, to the clinical efficacy of the atypical antidepressant trazodone.
>
> PMID: 15888508 [PubMed - in process]
>
> Seems that trazodone is more a 5-HT-1 agonist than an serotonine reuptake inhibitor - similar to buspirone!
Unfortunately mCPP is also a potent agonist at the 5-HT2C receptor, and can actually cause one to become anxious and agitated. Perhaps this is masked by some of the other actions trazodone possesses. I wish gepirone, another 5-HT1a agonist, had made it to market. It might have been a useful tool as an adjunct to antidepressants. On its own, though, I guess it just didn't cut it. The metabolite of this drug, and that of buspirone (1-PP), are the same and are capable of antagonizing NE alpha-2 receptors much like Remeron. Stoopid FDA.
- Scott
Posted by Sarah T. on May 22, 2005, at 21:45:41
In reply to Re: Trazodone = 5-HT-1 agonist (similar to buspirone), posted by SLS on May 22, 2005, at 7:40:37
Hi Scott,
I forgot, have you taken buspirone? If so, can you tell me about your experience with it?
S.
Posted by SLS on May 23, 2005, at 7:59:26
In reply to Re: Trazodone = 5-HT-1 agonist (similar to buspirone) » SLS, posted by Sarah T. on May 22, 2005, at 21:45:41
> Hi Scott,
>
> I forgot, have you taken buspirone? If so, can you tell me about your experience with it?
>
>
> S.No, I haven't tried it yet. I asked my last doctor if it were worth trying. He said no. He is a professor at NYU. It is the NYU algorithm that includes it in their treatment for refractory depression. I guess I should add it back to my list.
Thanks.
- Scott
Posted by Sarah T. on May 23, 2005, at 22:47:32
In reply to Re: Trazodone = 5-HT-1 agonist (similar to buspirone) » Sarah T., posted by SLS on May 23, 2005, at 7:59:26
Hi Scott,
Ah, so you're a fellow New Yorker. There are some good restaurants near NYU Medical Center, which is good to know if you're hungry after your medical appointments!
Thanks for the information on Buspar. I'm interested in trying it at some point; however, I must admit that I've never seen anyone terribly enthusiastic about it.
S.
Posted by ben on May 24, 2005, at 1:16:17
In reply to Trazodone = 5-HT-1 agonist (similar to buspirone), posted by ben on May 22, 2005, at 2:12:28
WHat is going on wyth gepirone? Does Organon trying a second time to approve it or do they stopped the developement of gepirone?
Posted by Questionmark on May 24, 2005, at 15:51:42
In reply to Re: Trazodone = 5-HT-1 agonist (similar to buspirone), posted by SLS on May 22, 2005, at 7:40:37
What pharmacological property of trazodone is it that makes you so drowsy? If it's not antihistaminic, it seems strange that it would do this so strongly. (i have never taken it.)
Posted by Ritch on May 24, 2005, at 23:12:16
In reply to Trazodone - what makes it so sedating?, posted by Questionmark on May 24, 2005, at 15:51:42
> What pharmacological property of trazodone is it that makes you so drowsy? If it's not antihistaminic, it seems strange that it would do this so strongly. (i have never taken it.)
I think it is the action at the alpha-1 adrenoreceptors. A lot of antipsychotics have this property. I got a stuffy nose while taking traz. and I also got that from taking Mellaril (an antipsychotic).
Posted by Questionmark on June 17, 2005, at 16:00:28
In reply to Re: Trazodone - what makes it so sedating? » Questionmark, posted by Ritch on May 24, 2005, at 23:12:16
This is the end of the thread.
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