Profiles of the Affinity of Antipsychotic Drugs for Neurotransmitter Receptors and Their Clinical Implication.

Yonemura, Keiichi; Miyanaga, Kazuo; Machiyama, Yukiteru

doi:10.2974/kmj.48.87

Cited by 15 publications

(10 citation statements)

References 24 publications

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“…Affinities for the dopaminergic receptors are also provided. (Kuoppamäki et al, 1995;Yonemura et al, 1998;Glennon, 2003;Kusumi et al, 2015). similar (≈10 nM).…”

Section: -Ht 7 Antagonists and Hiccupsmentioning

confidence: 74%

“…Chlorpromazine (Ki ≈ 840 nM), for all practical purposes, has no effect at the 5-HT 1A receptor (Yonemura et al, 1998).…”

Section: Anxiolytic Azapironesmentioning

confidence: 99%

“…There are numerous anecdotal reports in the non-scientific literature claiming that setrons cause hiccups ( Wilkes, 2007 ; Kantrowitz, 2009 ; MylanPharmaceuticals, 2017 ; Pharmacorama, 2017 ). Chlorpromazine has a very low affinity for this receptor ( Yonemura et al, 1998 ). Taken together, these data suggest that 5-HT 3 antagonists may facilitate singultus.…”

Section: Purpose Of the Workmentioning

confidence: 99%

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The Role of Serotonin in Singultus: A Review

Petroianu

Lorke

2020

Front. Neurosci.

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The use of dopamine receptor blockers for chronic singultus treatment is basedat least partially-on circular thinking: chlorpromazine is FDA-approved for hiccups, chlorpromazine is a neuroleptic, neuroleptics are dopamine receptor blockers, and therefore hiccup is due to dopaminergic dysfunction. Chlorpromazine interacts with high affinity with a multitude of receptors and ion channels. This promiscuity is the basis for many of the therapeutic effects and adverse drug reactions of this drug. While an involvement of dopamine is certain, it is by no means clear that dopaminergic dysfunction is the hallmark of singultus. The common denominator of most remedies for transient hiccup is their ability to activate the vagus nerve. Both afferent and efferent vagal activity and the central integration of the Xth cranial nerve function are modulated, inter alia, via serotonergic mechanisms; beneficial (therapeutic) effects for hiccup are to be expected from serotonin (5-HT) receptor subtype ligands that enhance vagal activity. Taken together, it appears that the ability to increase vagus output is mainly associated with 5-HT 1A , 5-HT 3 , and 5-HT 7 agonists and with 5-HT 2C antagonists. The plausibility of the serotonergic singultus hypothesis is examined against available pharmacokinetic, pharmacodynamic, and clinical data for a number of drugs.

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“…Affinities for the dopaminergic receptors are also provided. (Kuoppamäki et al, 1995;Yonemura et al, 1998;Glennon, 2003;Kusumi et al, 2015). similar (≈10 nM).…”

Section: -Ht 7 Antagonists and Hiccupsmentioning

confidence: 74%

“…Chlorpromazine (Ki ≈ 840 nM), for all practical purposes, has no effect at the 5-HT 1A receptor (Yonemura et al, 1998).…”

Section: Anxiolytic Azapironesmentioning

confidence: 99%

Section: Purpose Of the Workmentioning

confidence: 99%

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The Role of Serotonin in Singultus: A Review

Petroianu

Lorke

2020

Front. Neurosci.

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“…Thus, higher pKi values correspond to lower Ki values, and vice versa. 1 However, we suppose that sometimes a mix-up can occur between different measures of receptor-binding affinity. For instance, in a review 2 published in 2010, Ki values for asenapine are reported as follows: D2 (8.9), 5-HT1A (8.6), 5-HT2A (10.15), 5-HT2C (10.46), α1 (8.9), H1 (9.0), M1 (5.09), while in a previous paper 3 the same numerical values described in the review mentioned above are presented as pKi, not Ki: D2 (8.9), 5-HT1A (8.6), 5-HT2A (10.2), 5-HT2C (10.5), α1 (8.9), H1 (9.0), M1 (5.09).…”

mentioning

confidence: 99%

“…Proper knowledge of binding affinity profiles is decisive to: predicting the specific efficacy of a drug on positive (e.g., antagonism and low Ki to D2), negative (e.g., high 5-HT2A/D2 ratio), and cognitive (e.g., antagonism and low Ki to 5-HT7) symptoms of schizophrenia; considering a dimensional pharmacotherapeutic approach, rather than a strictly categorical one; detecting specific propensity to trigger extrapyramidal symptoms, hyperprolactinemia, sexual dysfunctions, sedative/metabolic, and antiadrenergic/anticholinergic/antihistaminergic effects; defining the best switching strategies between different antipsychotics, choosing among abrupt switch, taper switch, cross-taper switch, or plateau-cross-taper switch; predicting dopaminergic/adrenergic/cholinergic/serotonin/histamine rebound; determining the potential pharmacodynamic synergy of antipsychotic polypharmacy to choose a suitable complementary affinity profile; applying results of preclinical pharmacology studies to humans; using pharmacoepidemiologic-pharmacodynamic methods to investigate the mechanisms of adverse drug reactions recorded in pharmacovigilance databases; understanding the pharmacodynamic factors involved in pharmacogenomic-directed therapeutics; and orientating clinicians toward precision medicine. 1 - 5 …”

mentioning

confidence: 99%