PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Methoxydimethyltryptamines”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources
PubMed1981

Morphological and functional studies on the serotoninergic innervation of the inferior olive.

The inferior olive of the cat has, with fluorescence histochemistry, been shown to receive a rich serotoninergic innervation. The distribution of this innervation agrees with the topography of spinal afferent termination as well as the olivo-cerebellar climbing fiber projection. This indicates that different olivary compartments are under different serotoninergic influence. The serotoninergic innervation of the dorsal accessory nucleus (DAO) of the inferior olive of the rat has been identified with electron microscopic radioautography after labelling with 3H-serotonin. The serotoninergic varicosities contain microcanaliculi, tubular-vesicular organelles and large granular vesicles. Few of the serotoninergic varicosities engage in typical synaptic junctions. However, non-junctional varicosities often display other ultrastructural indications of polarity and directed transmitted release. Electrophysiological results indicate that the harmaline-induced tremor, as well as the tremor component of the "serotonin-syndrome", depends on the serotoninergic innervation of the inferior olive. Thus, the sensitivity of different olivary compartments to the induction of rhythmic, synchronous activity by harmaline parallels the distribution of serotoninergic innervation. Neurotoxic destruction of the serotoninergic innervation leads to decreased sensitivity to harmaline. Further, the serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine, as well as monoamine oxidase inhibition + L-tryptophan loading, leads to rhythmic mass climbing fiber activity in the cerebellum and whole body tremor. A neuromodulatory effect of serotonin on the olivary action potential mechanisms is proposed.

5,6-Dihydroxytryptamine↗
PubMed1984

Serotonin regulation of the canine migrating motor complex.

A potential role for endogenous serotonin (5-hydroxytryptamine) in the control of the migrating motor complex (MMC) was investigated in 10 conscious dogs. Strain gage force transducers or silver bipolar recording electrodes were sewn along the small intestine to record motor or myoelectrical patterns of activity, respectively. After an 18-hr fast, serotonin stimulated phase II-like circular muscle contractions when administered during phase I of the MMC. Methysergide produced a prolonged atropine-resistant increase in the number of contractions throughout the jejunum and ileum, thus suggesting agonist activity. Phase III contractions were not apparent during the methysergide-induced contractile activity. Cyproheptadine blocked the initiation and the migration of MMCs along the small intestine and significantly increased the period of the MMC. 5-methoxy-N,N-dimethyltryptamine also increased the period of the jejunal MMC. Pretreatment with parachlorophenylalanine reduced qualitatively the contractile amplitude and appearance of phases II and III of the MMC and significantly reduced the MMC period in two of four dogs. In conclusion, endogenous serotonin affects motor activity during MMC phases II and III and appears to be a candidate regulator of the intrinsic mechanisms governing the initiation and propagation of the canine MMC.

Animals↗
PubMed1981

Pharmacological studies on serotonin-mediated behaviour.

1. Administration to rats of a monoamine oxidase inhibitor (for example tranylcypromine: Tcp) followed by L-tryptophan increases the rate of synthesis and release of 5-hydroxytryptamine (5-HT) and results in a series of behavioural changes, some of which can be recorded on activity meters or scored. Various putative 5-HT agonists and the releasing drugs, fenfluramine and p-chloroamphetamine, also produce these changes. 2. A supersensitive behavioural response was produced by specific lesioning or p-chlorophenylalanine pretreatment and lesioning and sectioning experiments suggested several of the behaviours to be either hind-brain or spinally mediated. 3. A role for dopamine and GABA in the behaviour was demonstrated, but depletion of brain noradrenaline by specific lesioning or administration of disulfiram did not influence the behavioural changes. 4. The behaviour produced by administration of Tcp/L-tryptophan or 5-methoxy N,N-dimethyl tryptamine was inhibited by the suggested 5-HT antagonists, methysergide, methergoline and (--)-propranolol, but not by cinanserin, mianserin and cyproheptadine, other putative antagonists. In contrast, all the antagonists inhibited the behaviour when it was produced by injection of the agonist, quipazine. 5. The possible reasons for these differences is discussed in the light of the receptor binding characteristics of the drugs and the possible existence of different 5-HT receptor populations.

Animals↗
PubMed1983

Reciprocal changes in the firing rate of neostriatal and dorsal raphe neurons following local infusions or systemic injections of D-amphetamine: evidence for neostriatal heterogeneity.

A local infusion of d-amphetamine (d-AMPH) into the dorsal raphe nucleus (DRN) inhibited neuronal activity in this site and produced a mirror-image excitation in the ventrolateral, but not dorsomedial, neostriatum. This effect, which was mimicked by 5-methoxy-N,N-dimethyltryptamine, a serotonin autoreceptor agonist, was not altered by pretreatment with alpha-methyl-p-tyrosine. Similar regional differences in neostriatal activity were obtained following an electrolytic lesion of the DRN or an intraperitoneal injection of d-AMPH. In fact, whereas 1.0 mg/kg of d-AMPH accelerated ventrolateral activity and inhibited dorsomedial neurons, 7.5 mg/kg produced the opposite effect. At both doses, however, DRN activity was inversely related to firing rate in the ventrolateral, but not dorsomedial, neostriatum. These results indicate that only certain regions of the neostriatum are responsive to changes in DRN activity and that these regions respond differently to systemic injections of d-AMPH than other neostriatal sites.

Animals↗
PubMed1980

[Extraction of serotonin, bufotenin, 5-methoxytryptamine and 5-methoxy-N,N-dimethyltryptamine and their fluorometric determination with o-phthaldialdehyde].

For the investigated indolamines, the recovery following extraction with n-butanol and acetic acid ethyl ester from alkaline solution amounted to 80-90%. Using benzene only the two 5-methoxyindolamines were transferred from the alkaline medium into the organic phase. The reaction of the o-phthaldialdehyde with substituted indolamines was optimized in regard to higher fluorimetric detection sensitivity. The lower limit of determination was 2.0 ng for 5HT and 5OHDMT, and 1.0 ng for 5MeOT and 5MeODMT.

5-Methoxytryptamine↗
PubMed1980

An evaluation of the mechanism by which serotonergic activation depresses respiration.

The present investigation attempted to determine if the previously reported depression of respiration by serotonergic agonists was a result of peripheral or central nervous system drug effects. Systemic administration of 5-hydroxytryptophan (5-HTP) to pargyline-treated animals and 5-methoxy-N,N-di-methyltryptophan (5-MDMT) probably depress respiration secondary to central penetration of these drugs, since: 1) adult rats with biochemical evidence of partial destruction of central serotonergic neurons after neonatal intracisternal 5,7-dihydroxytryptamine were supersensitive to the respiratory depressing effect of 5-HTP and 5-MDMT; 2) the ventilatory effect of the serotonergic agonists was not reduced by surgical deafferentiation induced by bilateral transection of the glossopharyngeal nerves; 3) after sectioning of the vagus nerve, the absolute change produced by serotonergic agonists was less; however, the relative change was unaltered; and 4) inhibition of peripheral aromatic amino acid decarboxylase by RO-4-4602 significantly blunted the respiratory depressant activity of 5-HTP observed at 15 min but not that present 30 min after 5-HTP. The present fidings thus suggest that the cenvel by the activity of central serotonergic neurons.

5,7-Dihydroxytryptamine↗
PubMed1981

[Effects of peripheral electric stimulation on the central 5-hydroxytryptamine in mice: relation to the peripheral stimulation-produced analgesia (author's transl)].

Effects of peripheral electric stimulation (PES) on the functional state of central 5-hydroxytryptamine (5-HT) and on the analgesic effect were investigated in mice. The PES was administered by a passing rectangular wave (0.45 mA, 5 msec, 5-100 Hz) for 2 hr through bipolar electrodes implanted subcutaneously at the base of the tail. Whole brain 5-HT concentration remained unchanged with the PES at 20 Hz, whereas 5-hydroxy-indoleacetic acid concentrations were significantly increased in the whole brain. A significant increase in the whole brain compared with that in control was already attained at 30 min after initiation of the PES. Number of head-twitches induced by 5-methoxy-N,N-dimethyltryptamine after the PES was clearly potentiated. Increase in the number of head-twitches after the PES was abolished by administration of p-chlorophenylalanine, a 5-HT depletor, and 5,6-dihydroxytryptamine, a 5-HT neurotoxin. The PES for 1 hr produced an antinociceptive effect. Administration of L-5-hydroxytryptophan enhanced the antinociceptive effect induced by PES, while methysergide and naloxone completely abolished this antinociception. Thus, 5-HT neurons are probably excited functionally by the PES, and the mechanisms of analgesia produced by the PES involve both endogenous opiate systems and central serotonergic mechanisms.

5-Hydroxytryptophan↗
PubMed1982

Inhibition of phrenic and sympathetic vasomotor neurons in cats by the serotonin analog 5-methoxy-N,N-dimethyltryptamine.

5-Methoxy-N,N-dimethyltryptamine (20-200 microgram/kg) inhibits phrenic and sympathetic neural discharges and depresses blood pressure. The effects occur within seconds after injection. Complete recovery occurs, on the average, after 20 min. The inhibition of phrenic nerve discharges is prevented during hypercapnia and hyperthermia and reversed during 50 Hz electrical stimulation of the carotid sinus nerve. Cinanserin (2-4 mg/kg) antagonize the inhibition of phrenic nerve activity. Inhibition of sympathetic activity by 5MeODMT is also reversed during 50 Hz carotid sinus nerve stimulation, but is unaltered by hypercapnia, hyperthermia or cinanserin. High doses of 5MeODMT (200-700 microgram/kg i.v.) produce an initial apneustic discharge which is followed by inhibition of phrenic discharges. The inhibitory effects of 5MeODMT are attributed to a direct agonist action on central nervous serotonin receptors. The inhibition of phrenic and sympathetic neurons appears to be mediated by different types of serotonin receptors.

Animals↗
PubMed1982

Serotonin receptor sensitivity after acute and chronic treatment with mianserin.

The chronic administration of mianserin for 14 days leads to a marked decrease in the maximal number of serotonin2 (5-HT2) binding sites in brains of rats and mice with no change in the KD values. The decrease in [3H]spiroperidol binding to the 5-HT2 site in rats was most pronounced in the frontal cortex with only minor changes in hippocampus and pons-medulla. The 5-HT1 site was largely unaffected. The decrease in the Bmax for 5-HT2 site also occurred after a single dose of mianserin, although mianserin was more potent when given chronically. Maximal inhibition of binding occurred with a chronic dose of 0.5 mg/kg. The greatest decrease was found 48 hr after single or repeated doses with a gradual return to normal levels within 10 days. The administration of mianserin also leads to a decrease in 5-methoxy-N,N-dimethyltryptamine-induced head twitches in mice assayed 48 and 96 hr after a single or repeated doses, which is presumably correlated with the decrease in the 5-HT2 binding site assayed in vitro.

Animals↗
PubMed1981

Alteration of aminophylline-induced respiratory stimulation by perturbation of biogenic amine systems.

Aminophylline-induced stimulation of respiration in halothane-anesthetized rats was abolished in rats given 6-hydroxydopamine and desmethylimipramine neonatally to selectively destroy central nervous system dopamine nerve terminals. The respiratory stimulation was also prevented by prior administration of dopamine receptor antagonists haloperidol and cisflupenthixol. The combination of apomorphine and aminophylline produced an additive stimulatory effect on respiration to values greater than those observed with either drug alone. Animals which received pargyline and 5,7-dihydroxytryptamine neonatally to selectively destroy central nervous system serotonin nerve terminals appeared to be more sensitive to the stimulatory effects of aminophylline on respiration when tested as adults. The depressant effect of 5-methoxy-N, N-dimethyl-tryptamine on respiration was slightly enhanced in the presence of aminophylline. These data suggest that the respiratory response to aminophylline is the summation of the effects of this drug on central nervous system dopamine on serotonin neuronal systems.

5,7-Dihydroxytryptamine↗
PubMed1993

[Differences in the action of serotonin 1A-receptor agonists on rotating behavior or rats with unilaterally raphe-lesioned rats].

The differences between buspirone and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced turning behaviour has been investigated in rats with unilateral lesions of the dorsal and/or medial raphe nuclei (DR, MR). 5-MeODMT caused a most intensive contralateral turning in rats with MR lesions and least intensive ones in rats with both MR and DR lesions. Effect of buspirone depended on specific raphe nuclei lesions. Rats with unilateral lesions of both raphe nuclei caused a high locomotor activity in stress situation--free run wheels, the lowest ones--rats with DR lesions.

Animals↗
PubMed1993

5-HT1A receptors and the tail-flick response. IV. Spinally localized 5-HT1A receptors postsynaptic to serotoninergic neurones mediate spontaneous tail-flicks in the rat.

The present study examined the location of the serotonin (5-HT)1A receptors mediating the induction of spontaneous tail-flicks (STFs) in the rat. Serotoninergic neurones were lesioned by i.c.v. administration of 5,7-dihydroxytryptamine, which depleted levels of 5-HT in the spinal cord and other CNS tissues by > 90% without affecting those of noradrenaline and dopamine. In lesioned rats, the ability of the 5-HT releasers, para-chloroamphetamine and methylenedioxymethamphetamine, to elicit STFs was abolished. In contrast, the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)- tetralin (8-OH-DPAT), continued to evoke STFs. In fact, its effect was significantly enhanced in lesioned as compared with sham animals. In (nonlesioned) rats with catheters chronically implanted at the lumbar spinal level, intrathecal 8-OH-DPAT dose-dependently evoked STFs. The action of 8-OH-DPAT was extremely rapid, being maximal within 1 min of injection. Whereas the 5-HT1B/C agonist, TFMPP, the 5-HT1C/2 agonist, DOI, and the 5-HT3 agonist, m-chlorophenylbiguanide, failed to elicit STFs, the action of 8-OH-DPAT was mimicked by several other 5-HT1A agonists: S 14671, 5-MeODMT and lisuride. These also showed a time-course with a rapid onset. Further, the highly hydrophilic 5-HT1A agonist, 5-carboxyamidotryptamine, which fails to pass the blood-brain barrier, likewise dose-dependently elicited STFs upon direct lumbar administration. In contrast, administered onto the cervical spinal cord, it was completely ineffective. Systemic administration of the 5-HT1A antagonists, BMY 7378 or (-)-alprenolol, but not of the 5-HT1C/2 antagonist, ritanserin, nor of the 5-HT3 antagonist, ondansetron, blocked STFs elicited by lumbar administration of 8-OH-DPAT. Conversely, lumbar (but not cervical) administration of BMY 7378 and (-)-alprenolol dose-dependently blocked the action of systemic 8-OH-DPAT. These data demonstrate that STFs in the rat are mediated by 5-HT1A receptors postsynaptic to 5-HT neurones and localized in the lumbar spinal cord. Further, they support the concept of a relationship between STFs and mechanisms of primary sensory (nociceptive) processing.

5,7-Dihydroxytryptamine↗
PubMed1993

Studies on the neuronal circuits involved in the discriminative stimulus effects of 5-hydroxytryptamine1A receptor agonists in the rat.

Rats were trained to discriminate 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.1 mg/kg i.p.) or 5-methoxy-N,N-dimethyltryptamine (5-OMe-DMT, 1.25 mg/kg i.p.), a selective and nonselective 5-hydroxytryptamine1A (5-HT, serotonin) receptor agonist, respectively, from saline in a two-lever procedure. The selective 5-HT1A receptor agonist ipsapirone substituted completely for 8-OH-DPAT (ED50, 1.52 mg/kg) and 5-OMe-DMT substituted partially for 8-OH-DPAT, whereas 8-OH-DPAT (ED50, 0.07 mg/kg) and ipsapirone (ED50, 4.15 mg/kg) substituted completely for 5-OMe-DMT. These results suggest that the discriminative stimulus properties of both 8-OH-DPAT and 5-OMe-DMT are 5-HT1A receptor mediated, although 5-OMe-DMT may involve an additional interaction with other 5-HT receptor subtypes. 5-OMe-DMT substituted for 8-OH-DPAT after application in the lateral ventricle (ED50, 3.0 micrograms/rat) and the dorsal raphe nucleus (DRN, 1.1 micrograms/rat). After application in the DRN (ED50 range, 1.4-5.0 micrograms/rat) and the median raphe nucleus (2.3 micrograms/rat), and after bilateral application into the CA-4 region of the dorsal hippocampus (4.1 micrograms/rat), 8-OH-DPAT also produced responding on the 8-OH-DPAT lever. Ipsapirone also substituted for 8-OH-DPAT after application into the DRN and the hippocampus (ED50S, 38 and 62 micrograms/rat, respectively). The 5-HT1A mixed agonist-antagonist (1-(2-methoxyphenyl) 4-[4-(2-pthalimido)butyl]piperazine, i.p. NAN-190) attenuated the discriminative stimulus effects of 8-OH-DPAT injected i.p. (0.1 mg/kg), into the DRN (10 micrograms) or into the hippocampus (2 x 10 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

High-affinity agonist binding is not sufficient for agonist efficacy at 5-hydroxytryptamine2A receptors: evidence in favor of a modified ternary complex model.

In this study, the relationship between high-affinity agonist binding and second messenger production was examined at native and mutant 5-hydroxytryptamine2A receptors. At native 5-hydroxytryptamine2A receptors all agonists, with the exception of quipazine, discriminated between high- and low-affinity states of the receptor, as determined by analysis of competition binding assays. There was no correlation between the ability of selected agonists to label the high-affinity agonist state and to augment phosphoinositide hydrolysis. Quipazine, which did not discriminate between the affinity states of the receptor, behaved as a full agonist. Similar results were obtained when a point mutation (F340L) of a highly conserved phenylalanine located in transmembrane domain VI was examined. With the F340L mutant, most of the agonists tested labeled significantly fewer high-affinity sites, compared with the native receptor. There was no significant relationship between high-affinity agonist binding and second messenger production. Bufotenine and 4-iodo-3,5-dimethoxyphenylisopropylamine labeled similar percentages of high-affinity agonist binding sites (22% vs. 26%), but 4-iodo-3,5-dimethoxyphenylisopropylamine behaved as a full agonist, whereas bufotenine was devoid of detectable agonist activity. The inability of selected agonists to activate phosphoinositide hydrolysis was not due solely to lower agonist affinity for the mutant receptor, because the binding affinity of quipazine was unchanged by the F340L mutation but quipazine had no detectable agonist activity at the mutant receptor. Our results demonstrate that the ability of an agonist to promote the high-affinity state of the 5-hydroxytryptamine2A receptor is not correlated with its ability to augment second messenger production. These results are consistent with recent models of G protein-receptor functioning (e.g., modified ternary complex model) that predict that additional transition states of the receptor-ligand complex are essential for agonist efficacy.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗