Acid Diethylamide Research Articles

Single-dose 1cp-LSD administration for canine anxiety: a pilot study

Anxiety affects 14–20% of dogs. Pharmacological treatments often fail. Psychedelics have shown to be useful for anxiety and depression in humans, but their veterinary use remains unexplored. We aimed to determine the effects of low-dose 1-cyclopropionyl-d-lysergic acid diethylamide (1cp-LSD) administered in a single dose to a dog, to observe the effect and establish the safety of the substance. The patient was a 13-year-old female dog, weighing 13 kg, mixed breed, and spayed. A total of 5 µg was administered orally, equivalent to 0.38 µg/kg. The animal has had a history of separation related behavioral problems throughout her life. To objectively assess the degree of anxiety in the dog, a validated scale was utilized. The trial was scheduled at the house where the animal lives. The owner was present throughout the experience. Informed consent was obtained prior to the assay. The trial began at 12:15 p.m. on January 10, 2024, lasting for 5 and a half hours. The response to anxiety-inducing stimuli was equally anxious during the first two hours. From that point onwards, a significant change in the animal’s behavior was observed, with no signs/mild signs of anxiety. The trial concluded without any adverse effects on the animal. The patient did not show signs of having a psychedelic experience. This is the first time that a study of this nature has been conducted and reported in the canine species. 1cp-LSD proved to be safe and exerted the desired effect on the animal’s behavior, significantly reducing the patient’s anxiety.

The use patterns of novel psychedelics: experiential fingerprints of substituted phenethylamines, tryptamines and lysergamides

BackgroundNovel psychedelics (NPs) are an expanding set of compounds, presenting new challenges for drug policy and opportunities for clinical research. Unlike their classical derivatives, little is known regarding their use profiles or their subjective effects.AimsThe purpose of this study was to compile usage patterns and adverse event rates for individual NPs belonging to each of three main psychedelic structural families. Targeting the most widely used representatives for each class, we expanded on their phenomenological distinctions.MethodsA two-part survey was employed. We investigated the prevalence of novel phenethylamines, tryptamine and lysergamides in NP users (N = 1180), contrasting the type and incidence of adverse events (AEs) using a set of logistic regressions. Honing in on 2–4-Bromo-2,5-dimethoxyphenyl)ethanamine (2C-B) (48.6%), 1-propionyl-lysergic acid diethylamide (1P-LSD) (34.2%) and 4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT) (23.1%), we examined their phenomenological separability using a gradient boosting (XGBoost) supervised classifier.ResultsNovel phenethylamines had the highest prevalence of use (61.5%) seconded by tryptamines (43.8%) and lysergamides (42.9%). Usage patterns were identified for 32 different compounds, demonstrating variable dosages, durations and a common oral route of administration. Compared to phenethylamines, the odds for tryptamines and lysergamides users were significantly less for overall physical AEs. No significant differences in overall psychological AEs were found. Overall model area under the curve (AUC) stood at 0.79 with sensitivity (50.0%) and specificity (60.0%) for 2C-B ranking lowest.ConclusionNP classes may hold distinct AE rates and phenomenology, the latter potentially clouded by the subjective nature of these experiences. Further targeted research is warranted.

Identification of 1-Butyl-Lysergic Acid Diethylamide (1B-LSD) in Seized Blotter Paper Using an Integrated Workflow of Analytical Techniques and Chemo-Informatics.

The rapid dispersion of new psychoactive substances (NPS) presents challenges to customs services and analytical laboratories, which are involved in their detection and characterization. When the seized material is limited in quantity or of a complex nature, or when the target substance is present in very small amounts, the need to use advanced analytical techniques, efficient workflows and chemo-informatics tools is essential for the complete identification and elucidation of these substances. The current work describes the application of such a workflow in the analysis of a single blotter paper, seized by Swedish customs, that led to the identification of a lysergic acid diethylamide (LSD) derivative, 1-butyl-lysergic acid diethylamide (1B-LSD). Such blotter paper generally contains an amount in the range of 30–100 ug. This substance, which is closely related to 1-propionyl-lysergic acid diethylamide (1P-LSD), seems to have only recently reached the drug street market. Its identification was made possible by comprehensively combining gas chromatography with mass spectrometry detection (GC–MS), liquid chromatography coupled with high-resolution tandem MS (LC–HR-MS/MS), Orbitrap-MS and both 1D and 2D nuclear-magnetic-resonance (NMR) spectroscopy. All the obtained data have been managed, assessed, processed and evaluated using a chemo-informatics platform to produce the effective chemical and structural identification of 1B-LSD in the seized material.

Theoretical Investigation on the Molecular Structure, Electronic, Spectroscopic Studies and Nonlinear Optical Properties of 5-bromo-1-(2-cyano-pyridin-4-yl)-1H-indazole-3-carboxylic acid diethylamide: a DFT and TD-DFT Study

Theoretical Investigation on the Molecular Structure, Electronic, Spectroscopic Studies and Nonlinear Optical Properties of 5-bromo-1-(2-cyano-pyridin-4-yl)-1H-indazole-3-carboxylic acid diethylamide: a DFT and TD-DFT Study

Return of the lysergamides. Part II: Analytical and behavioural characterization of N6 -allyl-6-norlysergic acid diethylamide (AL-LAD) and (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ).

Lysergic acid N,N-diethylamide (LSD) is perhaps one of the most intriguing psychoactive substances known and numerous analogs have been explored to varying extents in previous decades. In 2013, N6 -allyl-6-norlysergic acid diethylamide (AL-LAD) and (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ) appeared on the 'research chemicals'/new psychoactive substances (NPS) market in both powdered and blotter form. This study reports the analytical characterization of powdered AL-LAD and LSZ tartrate samples and their semi-quantitative determination on blotter paper. Included in this study was the use of nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), low and high mass accuracy electrospray MS(/MS), high performance liquid chromatography diode array detection and GC solid-state infrared analysis. One feature shared by serotonergic psychedelics, such as LSD, is the ability to mediate behavioural responses via activation of 5-HT2A receptors. Both AL-LAD and LSZ displayed LSD-like responses in male C57BL/6 J mice when employing the head-twitch response (HTR) assay. AL-LAD and LSZ produced nearly identical inverted-U-shaped dose-dependent effects, with the maximal responses occurring at 200 µg/kg. Analysis of the dose responses by nonlinear regression confirmed that LSZ (ED50 = 114.2 nmol/kg) was equipotent to LSD (ED50 = 132.8 nmol/kg) in mice, whereas AL-LAD was slightly less potent (ED50 = 174.9 nmol/kg). The extent to which a comparison in potency can be translated directly to humans requires further investigation. Chemical and pharmacological data obtained from NPS may assist research communities that are interested in various aspects related to substance use and forensic identification. Copyright © 2016 John Wiley & Sons, Ltd.

Synthesis, spectroscopic characterization and crystal structure of 5-bromo-1-(2-cyano-pyridin-4-yl)-1H-indazole-3-carboxylic acid diethylamide

The title compound 5-bromo-1-(2-cyano-pyridin-4-yl)-1H-indazole-3-carboxylic acid diethylamide, C18H16BrN5O, is prepared from 5-bromoindazole-3-carboxylic acid methylester. N1-arylation is carried out with 4-chloro-2-cyanopyridine and the resulting product is converted to diethylamide by reacting with thionyl chloride and diethylamine. The structure is identified from its FT-IR, 1H NMR, 13C NMR spectroscopy, elemental analysis data and unambiguously confirmed by single crystal X-ray diffraction studies. There are two symmetry independent molecules in the asymmetric unit with no significant differences in bond lengths and angles. The title compound crystallizes in the triclinic system, space group \(P\bar 1\), with a = 11.2330(2); b = 11.6130(2); c = 15.4710(3) A, α = 92.515(1)°; β = 109.956(1)°; γ = 107.199(1)°; V = 1788.45(6)A3 and z = 4. An intramolecular C-H…N hydrogen bond forms an S(6) ring motif in one of the unique molecules. In the crystal, two molecules are linked about a center of inversion by C-H…O hydrogen bonded dimers generating an R22(16) ring motif. The crystal packing is stabilized by C-H…N, C-H…O hydrogen bonds and π…π stacking interactions.

Design, synthesis and characterization of 1H-pyridin-4-yl-3,5- disubstituted indazoles and their AKT inhibition activity

A new series of 1H-pyridin-4-yl-3,5-disubstituted indazoles and their derivatives were synthesized by the reaction of 5-bromo-1-(2-cyano-pyridin-4-yl)-1H-indazole-3-carboxylic acid diethylamide with aryl boronic acids by Suzuki coupling reaction in the presence of Pd(OAc)2 and CsF. All the new compounds have been characterized by spectral data. The title compounds were subsequently evaluated for their Akt kinase activity. A new series of 1H-pyridin-4-yl-3,5-disubstituted indazoles and their derivatives were synthesized by the reaction of 5-Bromo-1-(2-cyano-pyridin-4-yl)-1H-indazole-3-carboxylic acid diethylamide with aryl boronic acids by Suzuki-Coupling reaction in the presence of Pd(OAc)2 and CsF.

Synthesis and EPR Studies of Copper Metal Complexes of Dyes Derived from Remazol Red B, Procino Yellow, Fast Green FCF, Brilliant Cresyl Blue with Copper Acetate Monohydrate

The synthesis and characterization of four new solid dye complexes, CuL2 (L= 2‐[2‐methoxy‐5‐(propane‐1‐sulfonyl)‐phenyl azo]‐naphthalen‐1‐ol, 5‐{[3‐(4,6‐dihydroxy‐[1,3,5]tri azine‐2‐ylamino)‐phenyl]‐hydrazones}‐1‐ethyl‐4‐methyl‐2,6‐dioxo‐1,2,5,6‐tetrahydro‐pyridine‐3‐carboxylic acid diethylamide, 4‐{bis‐[4‐(benzyl‐ethyl‐amino)‐phenyl]‐methyl}‐phenol and 7‐imino‐4‐methyl‐7H‐phenoxazine‐1,3‐diamine) is reported. The mode for ligand coordination has been determined by IR and EPR spectra. The carboxyl and amino group of dyes coordinates to the Cu(II) atom as a unidentate or as a chelating ligand.

Characteristics of residual organics in municipal solid waste incinerator bottom ash

Although heavy metals in bottom ash have been a primary issue in resource recovery of municipal solid waste incinerator residues in past decades, less studied are potentially toxic and odorous organic fractions that exist as they have not been completely oxidized during the mass burn process. Using supercritical fluid extraction (SFE) and soxtec extraction (SE) techniques, this study investigated the characteristics of un-oxidized organic residues contained in bottom ash from three municipal solid waste incinerators in Taiwan during 2008–2009. All together 99 organics were identified in bottom ash samples using gas chromatography-mass spectrometry (GC-MS). Among the identified organics, aromatic compounds were most frequently detected. No polycyclic aromatic hydrocarbons were extracted by SFE or SE. Several phthalates (e.g., phthalic acid isobutyl tridec-2-yn-1-yl ester, dibutyl phthalate and 2-butoxyethyl butyl benzene-1,2-dicarboxylate), organic phosphates (e.g., octicizer and phosphoric acid isodecyl diphenyl ester), and aromatics and amines including pyridine, quinoline derivatives, chloro- and cyano-organics were successfully extracted. Aromatic amines (e.g., 1-nitro-9,10-dioxo-9,10-dihydro-anthracene-2-carboxylic acid diethylamide and 3-bromo-N-(4-bromo-2-chlorophenyl)-propanamide) and aromatic compounds (other than amines) (e.g., 7-chloro-4-methoxy-3-methylquinoline and 2,3-dihydro-N-hydroxy-4-methoxy-3,3-dimethyl indole-2-one) are probably the major odorous compounds in bottom ash. This work identifies organic pollutants in incinerated bottom ash that have received far less attention than their heavy metals counterpart.

The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series

Cluster headache (CH) is a stereotyped primary headache characterized by strictly unilateral severe orbital or periorbital pain and categorized as either episodic or chronic (1,2). Its prevalence is 0.1% (3). Oxygen and sumatriptan are the treatments of choice for individual attacks, whereas verapamil, lithium, corticosteroids and other neuromodulators can suppress attacks during cluster periods (1). All standard medication treatments may be ineffective. Surgical treatment may be an option for medication non-responders, including deep brain (4) or occipital nerve stimulation (5). However, serious complications from brain surgery, including death, can occur (6). An Internet survey of 53 CH patients reported on claims that psilocybin is better at aborting acute attacks than either oxygen or sumatriptan and that LSD and psilocybin are both better at triggering and extending remission than standard drugs (7). However, due to hallucinogenicity and the absence of established medical indication, these drugs are criminalized and placed within the most restrictive Schedule I of the Controlled Substances Act, which sanctions only limited research use. Although the hallucinogenic properties of LSD and psilocybin are undesirable from both regulatory and patient safety perspectives, it was unclear to us at the outset whether a non-hallucinogenic analog could also provide meaningful relief to CH patients. To address the question of whether the CH relief associated with these two structurally diverse compounds is related to the mechanisms triggering intoxication, we decided to investigate the efficacy of a nonhallucinogenic analog of LSD. LSD’s hallucinogenic effects are completely lost when the double bond in the D ring is saturated and with substitution at R2 (e.g. by bromination in 2-bromo-LSD) (BOL-148) (8). BOL-148 has been studied in volunteers (up to 20mg per os) (9) and in patients suffering from vascular headaches but not, apparently, in patients with CH (9,10). These past studies concluded that BOL-148 is non-toxic and non-hallucinogenic. Only very mild side effects, if any, have been observed, when given in the dose range used in our project (30mg/kg/body weight) (9). No long-term behavioral or psychological effects from BOL-148 have been reported from past studies with more than 300 healthy, normal subjects (11), and 30mg BOL-148 administered daily over four to five weeks failed to alter active psychosis in chronically ill schizophrenic women (12).

JNJ-20788560 [9-(8-Azabicyclo[3.2.1]oct-3-ylidene)-9H-xanthene-3-carboxylic Acid Diethylamide], a Selective Delta Opioid Receptor Agonist, Is a Potent and Efficacious Antihyperalgesic Agent That Does Not Produce Respiratory Depression, Pharmacologic Tolerance, or Physical Dependence

Mu-opioid analgesics are a mainstay in the treatment of acute and chronic pain of multiple origins, but their side effects, such as constipation, respiratory depression, and abuse liability, adversely affect patients. The recent demonstration of the up-regulation and membrane targeting of the delta-opioid receptor (DOR) following inflammation and the consequent enhanced therapeutic effect of delta-opioid agonists have enlivened the search for delta-opioid analgesic agents. JNJ-20788560 [9-(8-azabicyclo-[3.2.1]oct-3-ylidene)-9H-xanthene-3-carboxylic acid diethylamide] had an affinity of 2.0 nM for DOR (rat brain cortex binding assay) and a naltrindole sensitive DOR potency of 5.6 nM (5'-O-(3-[(35)S]thio)triphosphate assay). The compound had a potency of 7.6 mg/kg p.o. in a rat zymosan radiant heat test and of 13.5 mg/kg p.o. in a rat Complete Freund's adjuvant RH test but was virtually inactive in an uninflamed radiant heat test. In limited studies, tolerance was not observed to the antihyperalgesic or antinociceptive effects of the compound. Unlike ibuprofen, JNJ-20788560 did not produce gastrointestinal (GI) erosion. Although morphine reduced GI motility at all doses tested and reached nearly full effect at the highest dose, JNJ-20788560 did not retard transit at the lowest dose and reached only 11% reduction at the highest dose administered. Unlike morphine, JNJ-20788560 did not exhibit respiratory depression (blood gas analysis), and no withdrawal signs were precipitated by the administration of opioid (mu or delta) antagonists. Coupled with the previously published lack of self-administration behavior of the compound by alfentanil-trained primates, these findings strongly recommend delta-opioid agonists such as JNJ-20788560 for the relief of inflammatory hyperalgesia.

The Time-Course for Up- and Down-Regulation of the Cortical 5-Hydroxytryptamine (5-HT)2A Receptor Density Predicts 5-HT2A Receptor-Mediated Behavior in the Rabbit

5-Hydroxytryptamine (serotonin; 5-HT)2 receptor agonists such as (+/-)-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) injected systemically or directly into frontal cortex, elicit stereotyped head movements that are mediated by 5-HT2A receptors. Chronic administration of 5-HT2A receptor antagonists can produce either a down-regulation, e.g., d-2-bromolysergic acid diethylamide (BOL) or an up-regulation, e.g., alpha-phenyl-10(2-phenylethyl)-4-piperidinemethanol (MDL11,939) of cortical 5-HT2A receptors in the rabbit with no change in the density of the 5-HT2C receptor. We examined the degree to which the time course for the onset and offset of changes in cortical 5-HT2A receptor density was correlated with functional changes as measured by the magnitude of DOI elicited, 5-HT2A receptor-mediated head movements (head bobs). First, the magnitude of DOI-elicited head bobs was measured over 1 to 8 days after chronic BOL (5.8 micromol/kg), MDL11,939 (10 micromol/kg), or vehicle administration. Second, rabbits were injected with BOL, MDL11,939, or vehicle once daily for 8 days, and then, 1 to 8 days after the cessation of drug or vehicle, DOI-elicited head bobs were determined. Samples of frontal cortex were obtained for each animal immediately following behavioral testing, and 5-HT2A receptor density was measured using [3H]ketanserin. Thus, each animal provided a value for receptor density and number of head bobs, and these two measures showed a high degree of correlation between 0.94 for BOL and 0.95 for MDL11,939. This study establishes that the density of 5-HT2A receptors in cortex reflects their functional status.

Synthesis of 1‐(Substituted phenylcarbonyl/sulfonylamino)‐1,2,3,6‐tetrahydropyridine‐5‐carboxylic Acid Diethylamides as Potential Antiinflammatory Agents.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of 1-(Substituted Phenylcarbonyl/sulfonylamino)-1,2,3,6-tetrahydropyridine-5-carboxylic acid diethylamides as Potential Anti-inflammatory Agents.

Fifteen novel 1-(substituted phenylcarbonyl/sulfonylamino)-1,2,3,6-tetrahydro- pyridine-5-carboxylic acid diethylamide (7, 15) were synthesized in fair to good yields via sodium borohydride reduction of the corresponding 1-(substituted phenylcarbonyl/ sulfonylimino)-3-diethylcarbamoyl pyridinium ylides (6, 14) in absolute ethanol.

Cortical 5‐HT2A receptor density predicts 5‐HT2A receptor mediated behavior in the rabbit

Serotonin 5-HT2 receptor agonists such as DOI [1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane] injected systemically or directly into frontal cortex, elicit stereotyped head movements that are mediated by 5-HT2A receptors. Chronic administration of 5-HT2A receptor antagonists, can produce either a down-regulation, e.g., BOL (d-2-bromolysergic acid diethylamide) or an up-regulation (MDL11,939) of cortical 5-HT2A receptors in the rabbit with no change in the density of the 5-HT2C receptor. We examined the degree to which the time course for the onset and offset of changes in cortical 5-HT2A receptor density was correlated with functional changes as measured by the magnitude of DOI elicited, 5-HT2A mediated, head movements (head bobs). First, the magnitude of DOI elicited head bobs was measured at 1–8 days after chronic BOL (5.8 μmol/kg), MDL11,939 (10 μmol/kg) or vehicle administration. Second, rabbits were injected with BOL, MDL11,939 or vehicle once daily for 8 days and then, 1–8 days after the last drug or vehicle injection, DOI elicited head bobs were determined. Samples of frontal cortex were obtained for each animal immediately following behavioral testing, and 5-HT2A receptor density was measured using [3H]ketanserin. Thus, each animal provided a value for receptor density and number of head bobs and these two measures showed a high degree of correlation between of 0.94 for BOL and 0.95 for MDL11,939. This study establishes that the density of 5-HT2A receptors in cortex reflects their functional status. Supported by NIMH Grant MH16841-38 (JAH).

Potentiation of (DL)‐3,4‐methylenedioxymethamphetamine (MDMA)‐induced toxicity by the serotonin 2A receptior partial agonist d‐lysergic acid diethylamide (LSD), and the protection of same by the serotonin 2A/2C receptor antagonist MDL 11,939

AbstractTo elucidate the role of the serotonin (5‐HT)2A/2C receptors in 3,4‐methylenedioxymethamphetamine (MDMA)‐induced neurotoxicity, MDMA was administered to rats and the presence of the serotonin transporter (5‐HTT) was assessed at the protein level with immunohistochemistry (IHC), and the RNA level with a Northern blotting technique. d‐lysergic acid diethylamide (LSD) and MDL 11,939 were given in conjunction with MDMA in order to assess the importance of 5‐HT receptors in MDMA‐induced neurotoxicity. The hypothesis is that the MDMA + LSD‐treated animals should have more neurotoxicity as measured by loss of 5‐HTTs compared to the MDMA‐treated animals. Moreover, the loss of 5‐HTTs should be attenuated in animals given the combination of MDMA + MDL 11,939, as the latter drug is a selective 5‐HT2A/2C antagonist. The results showed that MDMA‐induced neurotoxicity was dose dependently increased by LSD. Moreover, the drug MDL 11,939 attenuated MDMA‐induced neurotoxicity, suggesting that 5‐HT2A/2C receptors are involved in MDMA‐induced neurotoxicity.

Effect of 5-HT2 receptor antagonists on a cranial nerve reflex in the rabbit: evidence for inverse agonism.

This study examined the role of the serotonin 5-HT2 receptor in motor function by examining the effect of antagonists on the motor performance of a cranial nerve reflex, the nictitating membrane (NM) reflex of the rabbit. The NM reflex was elicited by varying intensities of a tactile stimulus and the magnitudes of the elicited responses were measured at each intensity. Dose-response curves were obtained for the effects of several 5-HT2 receptor antagonists on response magnitude. d-Bro-molysergic acid diethylamide (BOL), LY-53,857 and ketanserin had no significant effect on the magnitude of the NM reflex, indicating that they are neutral antagonists. However, the 5-HT2 receptor antagonists ritanserin, MDL-11,939 and mianserin produced a significant reduction in response magnitude with no significant effects on response frequency, suggesting that they were acting as inverse agonists at the 5-HT2 receptor. The reduction in reflex magnitude produced by mianserin (10 micromol/kg) was fully blocked by BOL (5.8 micromol/kg), supporting the conclusion that mianserin was producing a reduction in reflex magnitude through an effect at the 5-HT2 receptor. The occurrence of inverse agonism suggests the possible existence of constitutive activity in vivo. We conclude that the 5-HT2 receptor (either 2A or 2C) plays an important role in motor function, perhaps by providing a tonic influence on motor systems.

Role of α1-adrenoceptors and 5-HT 2 receptors in serotonin-induced contraction of rat prostate: autoradiographical and functional studies

Urinary obstruction from benign prostatic hyperplasia is a common clinical problem possibly associated with excessive prostatic constriction around the urethra. These studies compared adrenergic and serotonergic functional activity to specific α 1 and serotonin (5-hydroxytryptamine; 5-HT) binding sites in the rat prostate. Isolated, left ventral lobes of the rat prostate were removed and examined for in vitro contraction. Norepinephrine-induced contraction of the rat prostate was competitively blocked by prazosin with an apparent antagonist dissociation constant (p K B) of 8.13. 5-HT also contracted the rat prostate. However, in the presence of prazosin, maximum 5-HT contraction was reduced by half suggesting that high concentrations of 5-HT can activate α 1 receptors in the prostate. The concentration-response curve to 5-HT in the presence of 1 μM prazosin was competitively inhibited by the 5-HT 2 receptor antagonist LY53857 (6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid 2-hydroxyl-1-methylpropylester ( Z)-2-butenedioate (1:1)) (p K B = 9.02). Autoradiographic studies with [ 125I]LSD (2-iodo-lysergic acid diethylamide) documented the presence of 5-HT 2 receptors since significant displacement of the radioligand occurred with 5-HT and LY53857, but not with prazosin. The α 1-adrenoceptor ligand [ 125I]HEAT ([β-(4-hydroxy-3-iodophenyl)ethyl-aminomethyl]-tetralone) confirmed the presence of α 1-adrenoceptors in the rat prostate since significant displacement of the radioligand occurred with prazosin, but not 5-HT or LY53857. The inability of prazosin to displace [ 125I]LSD and the inability of 5-HT to displace [ 125I]HEAT suggest that 5-HT cannot directly interact with α 1-adrenoceptors in the prostate. Thus activation of both α 1-adrenoceptors and 5-HT 2 receptors resulted in contraction of the rat prostate, and 5-HT-induced contraction was mediated by activation of 5-HT 2 receptors and the indirect activation of α 1-adrenoceptors.

Radioiodinated D-(+)-N1-ethyl-2-iodolysergic acid diethylamide: A ligand for in vitro and in vivo studies of serotonin receptors

Radioiodinated D-(+)-N1-ethyl-2-iodolysergic acid diethylamide ([125I]-EIL) has been evaluated as a ligand for in vitro and in vivo studies of cerebral serotonin 5-HT 2 receptors. [125I]-EIL exhibited high affinity (K D = 209 pM for 5-HT 2 receptors with a high degree of specific binding (80–95%) in membranes from rat prefrontal cortex. The regional distribution of [125I]-EIL binding in vivo to seven areas of mouse brain correlated significantly (R s = 0.93) with known densities of 5-HT 2 receptors. In vivo specificity, defined by tissue to cerebellum radioactivity ratios, reached a maximum for frontal cortex at 6 hr (21.2) and persisted through 16 hr (8.8). Ketanserin, a 5-HT 2 receptors antagonist, fully inhibited binding in a dose dependent fashion in all brain regions except cerebellum. By contrast, blockers for dopamine D 2, α- or β-adrenergic receptors did not significantly inhibit radioligand binding in any region. [125I]-EIL selectively labels 5-HT 2 receptors in vivo with the highest specificity of any serotonergic ligand reported to date, indicating that [123I]-EIL should prove applicable to single photon emission computed tomography studies in living brain.

Thioacylating agents as ultimate intermediates in the β-lyase catalysed metabolism of S-(pentachlorobutadienyl)-L-cysteine

The transformation of the hexachloro-1,3-butadiene metabolite S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-L-cysteine (PCBC) by bacterial cysteine conjugate β-lyase (β-lyase) and by N-dodecylpyridoxal bromide (PLP-Br) was investigated using GC/MS to identify products formed. PCBC was transformed by both bacterial β-lyase and PLP-Br to the major products 2,3,4,4-tetrachlorobutenoic acid and 2,3,4,4-tetrachlorothiobutenoic acid, and to the minor metabolites trichloroacetic acid and S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-mercaptoacetic acid. In the presence of diethylamine as model nucleophile, PLP-Br transformed PCBC to yield 2,3,4,4-tetrachlorothiobutenoic acid diethylamide; attempts to trap 1,2,3,4,4-pentachlorobutadienyl thiol, the initial metabolite formed by β-elimination from PCBC, were unsuccessful. The results obtained suggest that the formation of a thioacylating intermediate (a thioketene or a thiono acyl chloride) may be the decisive reaction during the β-lyase dependent activation of PCBC.