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PubMed2003

Backache, headache, and neurologic deficit after regional anesthesia.

Back pain, chemical backache, PDPH, and neurologic deficit all may be reported after regional anesthesia for childbirth. Back pain is common during pregnancy, but epidural analgesia during labor does not increase the incidence of long-term back pain. Chemical backache caused by 2-chloroprocaine is probably a result of hypocalcemic tetany of paraspinous muscles. The mechanism is presumed to be chelation of calcium by sodium bisulfite, an antioxidant present in nesacaine-MPF. PDPH after dural puncture is caused by leakage of CSF, which causes cerebral hypotension. Cerebral hypotension leads to traction on pain-sensitive intracranial structures and cerebral vasodilation. Initial therapy includes hydration, caffeine, and sumatriptan. EBP is the most effective treatment in severe PDPH. If the first EBP fails, a second blood patch can be performed. Neurologic deficits after regional anesthesia are rare. Meticulous technique and vigilance are the keystones in avoiding major neurologic complications of regional anesthesia. Rapid diagnosis and appropriate treatment are essential to optimize a successful outcome if complications do develop.

Analgesia, Epidural↗
PubMed2003

Permeability of porcine nasal mucosa correlated with human nasal absorption.

The Ussing chamber diffusion system was used as a model to study the apparent permeability across porcine nasal mucosa of eight drugs and molecules with different physicochemical characteristics, namely insulin, lidocaine, nicotine, PEG 4000, propranolol, sumatriptan, melagatran and an amino diether. A weak correlation was found between the apparent permeability coefficients and the corresponding literature data on the fraction absorbed after nasal administration in humans. In the case of passively transported drugs, a closer correlation was found than for the substances where other mechanisms such as carrier-mediated transport or possible efflux were involved. Factors influencing the correlation between in vitro and in vivo data are discussed and the importance of electrophysiological control of the viability status of the excised mucosa is emphasised. Although caution has to be exercised in view of the limitations of the in vitro system, it seems to be a useful tool when evaluating different factors influencing permeability of nasal mucosa.

Absorption↗
PubMed2001

Imidazoline-modified benzylimidazolines as h5-HT(1D/1B) serotonergic ligands.

Sumatriptan, a h5-HT1D and h5-HT1B receptor agonist used clinically as a migraine-abortive, produces certain side effects thought to result from its affinity for h5-HT1B receptors. The present investigation extends our work with benzylimidazolines as novel non-tryptamine h5-HT(1D/1B) ligands. The effect of N-methylation, N-benzylation, ring-aromatization, and variation of the imidazoline ring on affinity both at h5-HT1D and h5-HT1B receptors was examined. Several compounds were identified with good affinity and enhanced (i.e., > 100-fold) h5-HT1D versus hS-HT1B selectivity.

Benzyl Compounds↗
PubMed1998

Monitoring pregnancy outcomes following prenatal drug exposure through prospective pregnancy registries and passive surveillance: a pharmaceutical company commitment.

Objectives: Glaxo Wellcome (G.W.) becomes aware of prenatal exposures to its medications from as early as the clinical trial phase of development. An international process for monitoring prenatal exposure to all G.W. medicines has been developed utilizing a passive surveillance system and, for specific products, pregnancy registries. Additionally, G.W. jointly sponsors the multi-company Antiretroviral and North American Antiepileptic Drug (AED) Pregnancy Registries.Study Design: The registries are observational, case-registration and follow-up studies designed to detect evidence of teratogenicity associated with specific medications. Pregnancies are registered prospectively following prenatal exposure to the registry medication. An advisory committee for each registry reviews data and assists in dissemination of information. Committee members include independent scientists with expertise in fields such as obstetrics, teratology, epidemiology, pediatrics, and the relevant therapeutic areas.Results: The following data are from the prospective first-trimester exposures in each registry. Through December 1996, the proportion of outcomes in the Acyclovir Pregnancy Registry with birth defects (n = 17/505) is 3.4% (95% CI 2.0%, 5.4%). Through March 1997, the proportion of outcomes in the Lamotrigine Pregnancy Registry with birth defects (n = 4/76) is 5.3% (95% CI 1.7%, 13.6%). Through April 1997, the proportion of outcomes in the Sumatriptan Pregnancy Registry with birth defects (n = 5/148) is 3.4% (95% CI 1.3%, 8.1%). The newer Valacyclovir and Bupropion Pregnancy Registries have insufficient data for analysis. None of the registries have provided a risk estimate exceeding that expected in the general population, and no pattern of defects has been observed.Conclusions: The outcomes accumulated to date represent a sample of insufficient size for reaching conclusions regarding the possible teratogenic risk of using these drugs in pregnancy. Data obtained through these registries are shared with the medical community as a supplement to animal toxicology studies and to assist in weighing potential risks and benefits of treatment for individual patients. The success of the registries depends on the continued willingness of the OB/GYN community to notify the registries of prenatal exposures.

Journal Article↗
PubMed1995

The pharmacology of medications used in treating headache.

Migraine is a common and disabling disease of uncertain pathogenesis. Research on the trigeminovascular system, serotonin receptors, and substance P have provided clues to improving the pharmacotherapy of this disorder. Selective serotonin agonists, such as sumatriptan, dihydroergotamine, ergotamine tartrate, nonsteroidal anti-inflammatory drugs (NSAIDS), isometheptene mucate, and phenothiazines are useful to treat acute attacks. Prophylactic agents include beta-blockers, calcium channel blockers, NSAIDs, antidepressants, and valproate. The addition of several new agents for the acute and prophylactic therapy of migraine has improved the outlook for this debilitating disorder.

Adrenergic beta-Antagonists↗
PubMed2001

Characterization of 5-HT receptors in the parasitic nematode, Ascaris suum.

The pharmacological profiles of the 5-hydroxytryptamine (5-HT) receptors on Ascaris suum pharyngeal and somatic body wall muscles were investigated. The mechanisms involved following activation of these receptors were also studied. 5-HT activated and maintained pumping in isolated pharynxes with an EC-50 value of 44+/-1.7 microM. The 5-HT agonists, tryptamine, sumatriptan 8-OH-DPAT and 5-carboxyamidotryptamine all failed to stimulate pumping. The 5-HT2 antagonist, ketanserin, initially excited and then inhibited pumping while the 5-HT3 antagonist, ondansetron, had no effect. 5-HT and 5-HT agonists, 8-OH-DPAT, 5-carboxyamidotryptamine, alpha-methyl-5-HT and tryptamine all inhibited ACh-induced contractions of a somatic body wall muscle strip. Ketanserin partially blocked the inhibitory effect of alpha-methyl-5-HT and ACh-induced contractions while the 5-HT uptake blocker, fluoxetine, potentiated the effect of 5-HT on ACh-induced contractions. Basal levels of cAMP, 1540+/-232 pmol/mg, in pharyngeal muscle and 1721+/-134 pmol/mg, somatic body wall muscle, were both increased by forskolin. 5-HT had no effect on pharyngeal muscle cAMP levels but raised cAMP levels in somatic body wall muscle, e.g. 100 micron 5-HT, raised the level to 2851+/-212 pmol/mg and 1000 microM raised levels to 4578+/-1234 pmol/mg. 5-HT, 1000 microM, increased inositol phosphate levels in pharyngeal muscle. These results provide some evidence for a 5-HT2-like receptor on pharyngeal muscle. In contrast, the situation on somatic body wall muscle is more confusing since the pharmacological profile partly indicates a 5-HT2-like receptor but this receptor is linked to a rise in cAMP levels. Further studies are required to resolve the position but they must be based on the rational design of ligands specifically for nematode 5-HT receptors and not simply using ligands developed for the classification of mammalian 5-HT receptors. Such a design must take into account data from molecular biology studies of nematode 5-HT receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Pathophysiology of migraine--new insights.

Current theories propose that the primary dysfunction in migraine occurs within the CNS and that this evokes changes in blood vessels within pain-producing intracranial meningeal structures that give rise to headache pain. Migraine is now thought of as a neurovascular disorder. It has been proposed that genetic abnormalities may be responsible for altering the response threshold to migraine specific trigger factors in the brain of a migraineur compared to a normal individual. The exact nature of the central dysfunction that is produced in migraineurs is still not clear and may involve spreading depression-like phenomena and activation of brain stem monoaminergic nuclei that are part of the central autonomic, vascular and pain control centers. It is generally thought that local vasodilatation of intracranial extracerebral blood vessels and a consequent stimulation of surrounding trigeminal sensory nervous pain pathways is a key mechanism underlying the generation of headache pain associated with migraine. This activation of the 'trigeminovascular system' is thought to cause the release of vasoactive sensory neuropeptides, especially CGRP, that increase the pain response. The activated trigeminal nerves convey nociceptive information to central neurons in the brain stem trigeminal sensory nuclei that in turn relay the pain signals to higher centers where headache pain is perceived. It has been hypothesized that these central neurons may become sensitized as a migraine attack progresses. The 'triptan' anti-migraine agents (e.g. sumatriptan, rizatriptan, zolmitriptan naratriptan) are serotonergic agonists that have been shown to act selectively by causing vasoconstriction through 5-HT1B receptors that are expressed in human intracranial arteries and by inhibiting nociceptive transmission through an action at 5-HT1D receptors on peripheral trigeminal sensory nerve terminals in the meninges and central terminals in brain stem sensory nuclei. These three complementary sites of action underlie the clinical effectiveness of the 5-HT1B/1D agonists against migraine headache pain and its associated symptoms.

Brain↗
PubMed2004

A family-based association study of the 5-HT-1Dbeta receptor gene in obsessive-compulsive disorder.

Pharmacological studies have shown that sumatriptan, a selective ligand of the serotonin 5-HT-1Dbeta autoreceptor, modifies obsessive-compulsive disorder (OCD) symptoms. The current study analysed the G861C polymorphism of the 5-HT-1Dbeta gene in a sample of 72 trios. Genotyping data were analysed using the Family-Based Association Test (FBAT). We did not replicate the previously reported linkage disequilibrium between the G861 variant and OCD. However, a quantitative trait analysis, assessing severity of OCD symptoms and defined as YBOCS score, confirmed the finding that subjects with a preferential transmission of the G861 variant showed higher YBOCS Obsession scores compared to patients carrying the C861 allele. These preliminary findings may indicate that the 5-HT-1Dbeta receptor gene could be involved in the severity of obsession symptoms in OCD. However, it is important to perform the replication of these findings in larger sample sizes of informative families.

DNA↗
PubMed2006

Physiological studies of cortical spreading depression.

Cortical spreading depression (CSD) produces propagating waves of transient neuronal hyperexcitability followed by depression. CSD is initiated by K+ release following neuronal firing or electrical, mechanical or chemical stimuli. A triphasic (30-50 s) cortical potential transient accompanies localized transmembrane redistributions of K+, glutamate, Ca2+, Na+, Cl- and H+. Accumulated K+ in the restricted interstitial space can cause both further neuronal depolarisation and inward movement of K+ into astrocytes that buffers this increased extracellular K+ concentration ([K+])o. However, astrocyte interconnections may then propagate the CSD wave by K+ liberation through an opening of remote K+ channels by volume, Ca2+ or N-methyl-D-aspartate receptor activation. Changes in cerebral blood volume and in apparent water diffusion co-efficient (ADC) accompanying CSD were first studied using magnetic resonance imaging (MRI) in whole lissencephalic brains. Diffusion-weighted echoplanar imaging in gyrencephalic brains went on to demonstrate CSD features that paralleled classical migraine aura. The ADC activity persisted minutes/hours post KCl stimulus. Pixelwise analyses distinguished single primary events and multiple, spatially restricted, slower propagating, secondary events whose detailed features varied with the nature of the originating stimulus. These ADC changes varied reciprocally with T2*-weighted (i.e. referring to spin-spin relaxation times) waveforms reflecting local blood flow. There followed prolonged decreases in cerebral blood flow culminating in late cerebrovascular changes blocked by the antimigraine agent sumatriptan. CSD phenomena have possible translational significance for human migraine aura and other cerebral pathologies such as the peri-infarct depolarisation events that follow ischaemia and brain injury.

Animals↗
PubMed1995

Synthesis and serotonergic activity of arylpiperazide derivatives of serotonin: potent agonists for 5-HT1D receptors.

A series of new arylpiperazide derivatives of serotonin has been prepared and evaluated as 5-HT1D receptor agonists. Binding experiments at cloned human 5-HT1D alpha, 5-HT1D beta, and 5-HT1A receptors show that all the compounds are very potent and selective ligands for 5-HT1D receptor subtypes. Functional activity studies (contraction of the New Zealand white rabbit saphenous vein) demonstrate that most of the derivatives behave as full agonists. Among them, the aryl sulfonamide derivative 5q (pD2 = 8.33 compare to 5.75 for sumatriptan) was also identified as a very potent agonist in inhibiting the forskolin-mediated cyclase coupled to 5-HT1D beta receptors (EC50 = 0.52nM).

Animals↗
PubMed1994

Synthesis and biological activity of 3-[2-(dimethylamino)ethyl]-5-[(1,1-dioxo-5-methyl-1,2,5-thiadiazolidin- 2-yl)-methyl]-1H-indole and analogues: agonists for the 5-HT1D receptor.

A novel series of 5-(1,1-dioxo-1,2,5-thiadiazolidin-2-yl)tryptamines was designed, synthesized, and evaluated as 5-HT1D receptor agonists. Compounds such as 8d,f,k were identified which had comparable affinity, potency, and receptor selectivity to that of the antimigraine drug sumatriptan. Both 8d,k were found to be well absorbed in the rat with oral bioavailabilities of 66% and 62%, respectively. Additionally, 8d was found to be selective over other non-serotonergic receptors and exhibited relatively low central nervous system penetration.

Animals↗
PubMed1996

5-HT1D receptor agonist properties of novel 2-[5-[[(trifluoromethyl)sulfonyl]oxy]indolyl]ethylamines and their use as synthetic intermediates.

2-[5-[[(trifluoromethyl)sulfonyl]oxy]-1H-indol-3-yl]ethylamine (18), its N,N-di-n-propyl (12), N,N-diethyl (13), and N,N-dimethyl (14) derivatives, and 4-[3-[2-(N,N-dimethylamino)ethyl]-1H-indol-3-yl]-N-(p-methoxybenzyl) acrylamide (GR46611, 19) were synthesized and tested for binding affinities to cloned 5-HT1A, 5-HT1D alpha, 5-HT1D beta, and D2 receptors. In addition, the intrinsic efficacy was measured as the reduction of forskolin-stimulated cAMP in cells transfected with 5-HT1D alpha and 5-HT1D beta receptors in vitro. The 5-substituted indolyethylamines investigated displayed agonist activity at the 5-HT1D receptors with varying degrees of preference for the 5-HT1D alpha vs the 5-HT1D beta receptors. The primary amine and N,N-dimethyl substitution seemed to be optimal for 5-HT1D alpha affinity. Furthermore, the N,N-diethyl (13) and N,N-dimethyl (14) derivatives showed a 10-25 times preference for the 5-HT1D alpha vs the 5-HT1D beta receptor. In addition, all of the novel compounds showed affinity for the 5-HT1A receptor in vitro (Ki values ranging from 18 to 40 nM). The most promising derivative 14 was virtually devoid of central 5-HT1A agonist activity in rats, as determined by in vivo biochemical assays. Paradoxically, 14, like 19, induced a hypothermic response and a decrease in 5-HIAA levels in the prefrontal cortex and hypothalamus in guinea pigs after systemic administration. Sumatriptan failed to produce either of these effects due to a poor brain penetration.

5-Hydroxytryptophan↗
PubMed1996

Serotonin dimers: application of the bivalent ligand approach to the design of new potent and selective 5-HT(1B/1D) agonists.

A series of serotonin dimers of formula 4 in which two serotonin moeities are linked together through their 5-hydroxyl residue has been prepared and evaluated as 5-HT(1B/1D) receptor agonists. Binding experiments at cloned human 5-HT(1B), 5-HT(1D), and 5-HT(1A) receptors show that all of these dimers are very potent ligands at 5-HT(1B/1D) receptors with increased binding selectivity vs the 5-HT(1A) receptor when compared to serotonin. Studies of inhibition of the forskolin-stimulated c-AMP formation mediated by the human 5-HT(1B) receptor (formerly the 5-HT(1Dbeta) receptor) demonstrate that all of these serotonin dimers behave as full agonists. Among them, the piperazide derivatives of bis-serotonin, 4g,j, were also identified as very potent agonists in contracting the New Zealand white rabbit saphenous vein (pD2 = 7.6 in each case compared to 5.8 for sumatriptan). Results analysis supports the hypothesis that the important increase in potency of the serotonin dimers can be attributed to the presence of two serotonin pharmacophores in the same molecule, while the enhanced selectivity for 5-HT(1B/1D) receptor subtypes may be due to the position of the spacer attachment to serotonin.

Animals↗
PubMed1999

Synthesis and serotonergic activity of 3-[2-(pyrrolidin-1-yl)ethyl]indoles: potent agonists for the h5-HT1D receptor with high selectivity over the h5-HT1B receptor.

The design, synthesis, and biological evaluation of a novel series of 3-[2-(pyrrolidin-1-yl)ethyl]indoles with excellent selectivity for h5-HT1D (formerly 5-HT1Dalpha) receptors over h5-HT1B (formerly 5-HT1Dbeta) receptors are described. Clinically effective antimigraine drugs such as Sumatriptan show little selectivity between h5-HT1D and h5-HT1B receptors. The differential expression of h5-HT1D and h5-HT1B receptors in neural and vascular tissue prompted an investigation of whether a compound selective for the h5-HT1D subtype would have the same clinical efficacy but with reduced side effects. The pyrrolidine 3b was initially identified as having 9-fold selectivity for h5-HT1D over h5-HT1B receptors. Substitution of the pyrrolidine ring of 3b with methylbenzylamine groups gave compounds with nanomolar affinity for the h5-HT1D receptor and 100-fold selectivity with respect to h5-HT1B receptors. Modification of the indole 5-substituent led to the oxazolidinones 24a,b with up to 163-fold selectivity for the h5-HT1D subtype and improved selectivity over other serotonin receptors. The compounds were shown to be full agonists by measurement of agonist-induced [35S]GTPgammaS binding in CHO cells expressed with h5-HT receptors. This study suggests that the h5-HT1D and h5-HT1B receptors can be differentiated by appropriate substitution of the ligand in the region which binds to the aspartate residue and reveals a large binding pocket in the h5-HT1D receptor domain which is absent for the h5-HT1B receptor. The compounds described herein will be important tools to delineate the role of h5-HT1D receptors in migraine.

Administration, Oral↗
PubMed1999

3-(Piperazinylpropyl)indoles: selective, orally bioavailable h5-HT1D receptor agonists as potential antimigraine agents.

Clinically effective antimigraine drugs such as Sumatriptan have similar affinity at h5-HT1D and h5-HT1B receptors. In the search for a h5-HT1D-selective agonist as an antimigraine agent, a novel series of 3-(propylpiperazinyl)indoles have been synthesized and evaluated at h5-HT1D and h5-HT1B receptors. This class of compounds has provided subnanomolar, fully efficacious h5-HT1D agonists with up to 200-fold selectivity for the h5-HT1D receptor over the h5-HT1B receptor. Unlike other h5-HT1D-selective series, several propylpiperazines demonstrate good oral bioavailability. The optimum compound was 1-(3-[5-(1,2, 4-triazol-4-yl)-1H-indol-3-yl]propyl)-4-(2-(3-fluorophenyl)ethyl)p ipe razine (7f) which has excellent selectivity for h5-HT1D receptors over other 5-HT receptor subtypes and good oral bioavailability in three species. Compound 7f has been selected for further investigation as a potential development candidate in the treatment of migraine.

Administration, Oral↗
PubMed1999

N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist.

It has been observed that reported 5-HT1D receptor agonists have at least one heteroatom (N, O, or S) on the 5-substituent of the indole. This has led to the hypothesis that a 5-substituent capable of participating in hydrogen bonding is critical for conveying high affinity. This article describes the synthesis and biological evaluation of a new series of 5-alkyltryptamine analogues, which does not have a heteroatom in the 5-substituent group. In contrast to the hypothesis, 5-alkyltryptamines all exhibit high binding affinities for the human 5-HT1D receptor. The size of the lipophilic alkyl group at the 5-position of the indole has significant impact on the 5-HT1D binding affinity. Compounds with a tert-butyl group at the 5-position such as 9d, 10, and 11 were identified. These analogues display high binding affinity (Ki < 1 nM) and moderate receptor selectivity in comparison with known antimigraine agents such as sumatriptan, naratriptan, rizatriptan, and VML-251.

Cell Line↗
PubMed2001

Modeling and stimulation for clinical trial design involving a categorical response: a phase II case study with naratriptan.

PURPOSE: The overall aim of the present study was to investigate retrospectively the feasibility and utility of model-based clinical trial simulation as applied to the clinical development of naratriptan with effect measured on a categorical scale. METHODS: A PK-PD model for naratriptan was developed by using information gathered from previous naratriptan and sumatriptan preclinical and clinical trials. The phase IIa naratriptan data were used to check the PK-PD model in its ability to describe future data. A further PK-PD model was developed by using the phase IIa naratriptan data, and a phase IIb trial was designed by simulation with the use of Matlab. The design resulting from clinical trial simulation was compared with that derived by using D-optimal design. RESULTS: The PK-PD model showed reasonable agreement with the data observed in the phase IIa naratriptan clinical trial. Clinical trial simulation resulted in a design with four or five arms at 0 mg, 2.5 and/or 5 mg, 10 mg, and 20 mg, PD measurements to be taken at 0, 2, and 4 or 6 h and at least 150 patients per arm. A sub-D-optimal design resulted in two dosing arms at 0 and 10 mg and PD measurements to be taken at 1 and 2 h. CONCLUSIONS: Clinical trial simulation is a useful tool for the quantitative assessment of the influence of the controllable factors and is the only tool for the quantitative assessment of the uncontrollable factors on the power of a clinical trial.

Administration, Oral↗
PubMed1997

Identification of 5-hydroxytryptamine receptors positively coupled to adenylyl cyclase in rat cultured astrocytes.

1. 5-Hydroxytryptamine (5-HT) elicited a dose-dependent stimulation of intracellular adenosine 3': 5'-cyclic monophosphate (cyclic AMP) accumulation in cultured astrocytes derived from neonatal rat (Sprague Dawley) thalamic/hypothalamic area with a potency (pEC50) of 6.68 +/- 0.08 (mean +/- s.e. mean). 2. In order to characterize the 5-HT receptor responsible for the cyclic AMP accumulation the effects of a variety of compounds were investigated on basal cyclic AMP levels (agonists) and 5-carboxamidotryptamine (5-CT) stimulated cyclic AMP levels (antagonists). The rank order of potency for the agonists investigated was 5-CT (pEC50 = 7.81 +/- 0.09) > 5-methoxytryptamine (5-MeOT) (pEC50 = 6.86 +/- 0.36) > 5-HT (pEC50 = 6.68 +/- 0.08). The following compounds, at concentrations up to 10 microM, did not affect basal cyclic AMP levels 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), cisapride, sumatriptan, DOI and RU 24969. The rank order of potency of antagonists was methiothepin (pKi = 7.98 +/- 0.25) > mesulergine (pKi = 7.58 +/- 0.18) > ritanserin (pKi = 7.20 +/- 0.24) > clozapine (pKi = 7.03 +/- 0.19) > mianserin (pKi = 6.41 +/- 0.19). The following compounds, at concentrations up to 10 microM, were inactive: ketanserin, WAY100635, GR127935. This pharmacological profile is consistent with that of 5-HT7 receptor subtype-mediated effects. 3. The cultured astrocytes exhibited regional heterogeneity in the magnitude of cyclic AMP accumulation (Emax). Cells cultured from the thalamic/hypothalamic area had significantly higher Emax values (588 +/- 75% and 572 +/- 63% of basal levels for 5-CT and 5-HT, respectively) compared to brainstem (274 +/- 51% and 318 +/- 46%, respectively) and colliculus astrocytes (244 +/- 15% and 301 +/- 24%, respectively). No significant differences in pEC50 (for either 5-HT or 5-CT) values were observed. 4. Reverse transcriptase-polymerase chain reaction (RT-PCR) with primers specific for the 5-HT7 receptor confirmed expression of messenger RNA for this receptor subtype by the cultured astrocytes derived from all regions investigated. Primers specific for the 5-HT6 receptor also amplified a cDNA fragment from the same samples. 5. From these findings, we conclude that astrocytes cultured from a number of brain regions express functional 5-HT receptors positively coupled to adenylyl cyclase and that the level of receptor expression or the efficiency of receptor coupling is regionally-dependent. The pharmacological profile of the receptor on thalamic/hypothalamic astrocytes suggests that the 5-HT7 receptor is the dominant receptor that is functionally expressed even though astrocyte cultures have the capacity to express both 5-HT6 and 5-HT7 receptor messenger RNA.

Adenylyl Cyclases↗