piperidines and bemesetron

1-Benzylpiperazine (also known as 'Legal X', 'Legal E', or 'A2') is a psychoactive compound increasingly encountered on the clandestine market. Previous experimental data suggest that the compound possesses addictive properties. In the present study, we used the conditioned place preference method in the rat to test whether 1-benzylpiperazine possesses rewarding properties. Furthermore, the mechanisms of the 1-benzylpiperazine reward were investigated using selected dopamine and serotonin receptor antagonists. 1-Benzylpiperazine (1.25, 5, and 20 mg/kg) induced dose-dependently place preference. This place preference was attenuated by the antagonists SCH23390 (0.2 mg/kg; dopamine D1-like receptors) and MDL72222 (1.0 mg/kg; serotonin3 receptors), but not by raclopride (0.8 mg/kg; dopamine D2-like receptors) or ketanserin (2 mg/kg; preferentially serotonin2 receptors). Our results show that 1-benzylpiperazine possesses rewarding properties in the rat, which suggests the compound to be susceptible to human abuse. The brain dopaminergic and serotonergic systems appear to be involved in the 1-benzylpiperazine reward.

Topics: Animals; Behavior, Animal; Benzazepines; Conditioning, Psychological; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Ketanserin; Male; Piperidines; Psychotropic Drugs; Raclopride; Rats; Rats, Wistar; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Serotonin, 5-HT2; Receptors, Serotonin, 5-HT3; Reward; Serotonin 5-HT2 Receptor Antagonists; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Substance-Related Disorders; Tropanes

Methamphetamine (MAP) is one of the most commonly abused drugs in Asia, and previous studies suggest that serotonin 3 receptors (5-HT(3)) are involved in MAP-induced locomotion and reward. However, little is known about the role of 5-HT(3) receptors in MAP-induced behavioral sensitization. Here, we measured the effects of MDL 72222, a 5-HT(3) antagonist, and SR 57227 A, a 5-HT(3) agonist, on the development and expression of MAP-induced behavioral sensitization, and alternations of 5-HT(3) receptor binding labeled with the 5-HT(3)-selective antagonist, [(3)H]GR65630, in mice. In addition, we investigated the effects of MAP on 5-HT(3A) receptor channel activity in Xenopus laevis oocytes expressing 5-HT(3A) receptors. We found that MDL 72222 attenuated both the development and expression of behavioral sensitization to MAP (1.0 mg/kg, i.p.), and that this attenuating effect of MDL 72222 was reversed by pre-treatment with SR 57227 A. In oocytes expressing 5-HT(3A) receptor, MAP exhibited a dual modulation of 5-HT(3A) receptor channel activity, i.e. pre-treatment with a low dose of MAP (0.1 microm) enhanced 5-HT-induced inward peak current (I(5-HT)) but a high dose of MAP (100 microm) inhibited I(5-HT). The acute administration of MDL 72222 with MAP decreased [(3)H]GR65630 binding versus MAP alone in the mouse striatum. Our results suggest that MDL 72222 attenuates MAP-induced behavioral sensitization via 5-HT(3) receptors in the caudate putamen, and that 5-HT(3) receptor antagonists like MDL 72222 have potential as novel anti-psychotic agents for the treatment of MAP dependence and psychosis.

Topics: Algorithms; Animals; Autoradiography; Behavior, Animal; Dopamine Uptake Inhibitors; Imidazoles; Indoles; Male; Methamphetamine; Mice; Mice, Inbred ICR; Microinjections; Motor Activity; Oocytes; Piperidines; Receptors, Serotonin, 5-HT3; RNA, Complementary; Serotonin Antagonists; Serotonin Receptor Agonists; Tropanes; Xenopus laevis

Activation of vanilloid receptors has commonly been used to facilitate neurogenic inflammation and plasma exudation to model components of the pathogenesis of migraine; however, these studies have been performed mainly in species lacking the emetic reflex. In the present studies, therefore, we used Suncus murinus, a species of insectivore capable of emesis, to investigate if the vanilloid receptor agonist resiniferatoxin is capable of modeling the emesis associated with migraine. Resiniferatoxin (100 nmol/kg, s.c.) induced an emetic response that was antagonized significantly (P<0.05) by ruthenium red (1-3 micromol), (2R-trans)-4-[1-[3,5-bis(trifluromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-acetamide (S)-hydroxybutanedioate (R116301; 10-100 micromol/kg), and scopolamine (1 micromol/kg), but not by dihydroergotamine (0.3-3 micromol/kg), sumatriptan (1-10 micromol/kg), methysergide (1-10 micromol/kg), tropanyl 3,5-dichlorobenzoate (MDL72222; 3-30 micromol/kg), ondansetron (0.3-3 micromol/kg), metoclopramide (3-30 micromol/kg), domperidone (3-30 micromol/kg), diphenhydramine (1-10 micromol/kg), or indomethacin (3-30 micromol/kg). The failure of a wide range of representative anti-migraine drugs to reduce retching and vomiting limits the use of this model to identify/investigate novel treatments for the emesis (and nausea) associated with migraine attacks in humans. However, the results provide further evidence for the involvement of a novel vanilloid receptor in resiniferatoxin-induced emesis and implicate both tachykinins and acetylcholine in the pathway(s) activated by resiniferatoxin in S. murinus.

Topics: Animals; Antiemetics; Butanols; Capsaicin; Cyclooxygenase Inhibitors; Dihydroergotamine; Diphenhydramine; Diterpenes; Domperidone; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Humans; Indomethacin; Malates; Methysergide; Metoclopramide; Migraine Disorders; Ondansetron; Piperidines; Ruthenium Red; Scopolamine; Serotonin Antagonists; Serotonin Receptor Agonists; Shrews; Sumatriptan; Time Factors; Tropanes; Vomiting

The pharmacology of prejunctional serotonin (5-HT) heteroreceptors that regulate the release of norepinephrine (NE) was studied in isolated bovine and human iris-ciliary bodies. The effect of exogenous 5-HT and various 5-HT receptor agonists was examined on the release of [3H]-norepinephrine ([3H]NE). Both 5-HT and m-chlorophenyl-biguanide (m-CPBG) caused enhancement in the field-stimulated release of [3H]NE from bovine tissues whereas 5-carboxamidotryptamine (5-CT) had no such effect. On the other hand, 8hydroxy-dipropylaminotetralin (8-OH-DPAT), caused a significant dose-related inhibition of evoked [3H]NE release. In human iris-ciliary bodies, 5-HT caused an inhibitory response on electrically-evoked [3H]NE release at low concentrations but produced an excitatory action at concentrations greater than 3 microM. To further confirm the nature of the prejunctional 5-HT heteroreceptors regulating [3H]NE release, effects of 5-HT3, 5-HT6 and 5-HT7 receptor antagonists were examined on a standard response to 5-HT. All antagonists examined caused a concentration-dependent inhibition of the response elicited by the standard 5-HT-induced response with the following rank order of potency (as measured by IC30 values): MDL-72222 >> SB-258719 > RO-04-690. We conclude that the excitatory prejunctional 5-HT heteroreceptors present in bovine iris-ciliary bodies belong to the 5-HT3 receptor subtype.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Biguanides; Cattle; Ciliary Body; Dose-Response Relationship, Drug; Electric Stimulation; Humans; In Vitro Techniques; Iris; Norepinephrine; Piperidines; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Sulfonamides; Tritium; Tropanes

The pharmacological characterization of a 5-HT receptor-mediated contractile response in the mouse isolated ileum is described. In the presence of methysergide (1 microM), 5-hydroxytryptamine (5-HT, 0.3 - 100 microM) produced phasic concentration-dependent contractions of segments of the mouse isolated ileum with a pEC(50) value of 5.47+/-0.09. The 5-HT(3) receptor selective agonists m-chlorophenylbiguanide (0.3 - 100 microM, pEC(50) 5.81+/-0.04), 1-phenylbiguanide (3 - 100 microM, pEC(50) 5.05+/-0.06) and 2-methyl-5-HT (3 - 100 microM, pEC(50) 5.00+/-0.07) acted as full agonists to induce contractile responses. 5-methoxytryptamine (0.1 - 100 microM), RS 67506 (0.1 - 100 microM) and alpha-methyl-5-HT (0.1 - 100 microM) failed to mimic the 5-HT responses. The contractile response to 5-HT was not antagonized by either 5-HT(2) receptor antagonists ritanserin (0.1 microM) or ketanserin (1 microM) nor the 5-HT(4) receptor antagonist SB 204070 (0.1 microM). The 5-HT(3) receptor selective antagonists granisetron (0.3 - 1 nM), tropisetron (1 - 10 nM), ondansetron (10 nM - 1 microM) and MDL 72222 (10 nM - 1 microM) caused rightward displacement of the concentration-response curves to 5-HT. The lower concentrations of the antagonists caused approximate parallel rightward shifts of the concentration-response curves to 5-HT with apparent pK(B) values for granisetron (9.70+/-0. 39), tropisetron (9.18+/-0.20), ondansetron (8.84+/-0.24) and MDL 72222 (8.65+/-0.35). But higher concentrations of antagonists resulted in a progressive reduction in the maximum responses. The contractile response to 5-HT was abolished by tetrodotoxin (0.3 microM); atropine (0.1 and 1 microM) decreased the maximum response of the 5-HT concentration-response curve by approximately 65%. It is concluded that a neuronally located 5-HT(3) receptor mediates a contractile response to 5-HT in the mouse ileum. The 5-HT(3) receptor in the mouse ileum has a different pharmacological profile to that reported for the guinea-pig ileum.

Topics: Animals; Atropine; Dioxanes; Dose-Response Relationship, Drug; Female; Granisetron; Ileum; In Vitro Techniques; Indoles; Ketanserin; Male; Mice; Muscle Contraction; Ondansetron; Piperidines; Receptors, Serotonin; Ritanserin; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Tetrodotoxin; Tropanes; Tropisetron

The effects of ondansetron on the neuromuscular function of the guinea-pig ileum were investigated in vitro. Ondansetron, but not tropisetron or MDL 72222 (1alpha-H-3alpha-5alpha-H-tropan-3-yl-3,5-dichlo robenzoate), enhanced submaximal electrically induced contractions (EC50) = 1.3 x 10(-5) M). Desensitization with 5-hydroxytryptamine (1 x 10(-5) M) or 2-methyl-5-HT (1 x 10(-5) M) abolished this facilitatory response, which remained unaltered after desensitization with 5-methoxytryptamine (1 x 10(-5) M) or addition of tropisetron, MDL 72222, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan, SB203186 (1-piperidinylethyl-1H-indole-3 carboxylate hydrochloride), pirenzepine or hexamethonium. At higher concentrations, ondansetron decreased the electrically induced contractions (EC50 = 1 x 10(-4) M); the inhibitory response was unaffected by (-)-naloxone (1 x 10(-6) M) or idazoxan (1 x 10(-6) M). We conclude that, in the guinea-pig ileum, ondansetron elicits a biphasic response: facilitation of neuromuscular transmission mediated by a serotonergic receptor distinct from the 5-HT3, 5-HT4 or putative 5-HT1P receptors, and an inhibitory response that does not involve opiate or alpha2-adrenoceptors.

Topics: 5-Methoxytryptamine; Animals; Electric Stimulation; Guinea Pigs; Ileum; In Vitro Techniques; Indoles; Male; Muscle Contraction; Muscle, Smooth; Ondansetron; Piperidines; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Serotonin; Serotonin Antagonists; Synaptic Transmission; Tropanes; Tropisetron

Our work has focused on identifying the type of serotonin receptor through which serotonin acts as a developmental signal in the central nervous system. Previously, we have found that the regulation of development of ascending serotonergic neurons is through the balance of two serotonin receptors. One, the 5-HT1a receptor, releases a growth factor from astroglial cells. The other receptor is related to a release-regulating autoreceptor and can be stimulated indirectly by serotonin releasers such as fenfluramine. In the present study, we examined the receptors which regulate development of the descending neurons by treating pregnant rats with selective serotonergic drugs, from gestation day 12 until birth. Pups were subsequently tested for alterations in development by nociceptive testing (tail-flick latency) and by determining the binding of 3H-paroxetine, an indicator of serotonin terminal density, in spinal cord. Our results show that agents stimulating the 5-HT1a receptor (8-OH-DPAT) or the 5-HT1b receptor (TFMPP) or substances which release serotonin (fenfluramine) had no effect on the development of spinal serotonergic pathways. However, agents acting on the 5-HT3 receptor did--the agonist phenylbiguanide (PG) increased latency on tail-flick testing (postnatal days 10 and 30), while the antagonist, MDL 72222, decreased latency (postnatal days 10 and 18). Interestingly, both the agonist and the antagonist significantly increased 3H-paroxetine binding on postnatal day 18. Our results are discussed in terms of a possible mechanism by which 5-HT3 receptors may influence development.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Aging; Animals; Biguanides; Female; Fenfluramine; Hypoglycemic Agents; Maternal-Fetal Exchange; Neurons; Pain; Paroxetine; Piperazines; Piperidines; Pregnancy; Rats; Rats, Inbred Strains; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Spinal Cord; Tetrahydronaphthalenes; Tropanes

The interaction of 5-hydroxytryptamine (5-HT) with sympathetic transmission was investigated in the guinea pig inferior mesenteric artery (IMA) and ganglion (IMG). Intracellular recordings of membrane potential were made using glass microelectrodes. Superfusion of 5-HT (0.3 microM) reduced the amplitudes of stimulation-evoked excitatory junction potentials in the IMA. 5-HT had no effect on depolarizing responses to pressure-ejection of adenosine triphosphate or norepinephrine in the IMA. The inhibitory effect of 5-HT on excitatory junction potentials in the IMA was abolished by methysergide (3 microM), but was unaffected by the following antagonists: methiothepin (1 microM), MDL 72222 (3 microM), MDL 11939 (0.3 microM) or by phentolamine (10 microM). In the IMG, pressure-ejection of 5-HT (10 mM) evoked fast and slow depolarizing responses in 77% of neurons tested; the fast depolarizing responses to 5-HT were reduced in the presence of MDL 72222 (5 microM). Superfusion of 5-HT (0.3-3 microM) had no effect on stimulation-evoked fast excitatory postsynaptic potentials in the IMG. Thus, the results of the present study suggest that, depending on its site of interaction with postganglionic sympathetic neurons, 5-HT may have excitatory or inhibitory effects on sympathetic transmission. 5-HT may inhibit transmitter release through the activation of as yet unidentified 5-HT receptors on the sympathetic nerve endings in mesenteric blood vessels. Whereas, in the prevertebral ganglion, 5-HT may act to facilitate sympathetic transmission, in part, through activation of 5-HT3, receptors on the somata of principal neurons.

Topics: Animals; Cell Membrane; Female; Ganglia, Sympathetic; Guinea Pigs; Male; Membrane Potentials; Mesenteric Arteries; Methiothepin; Methysergide; Phentolamine; Piperidines; Serotonin; Serotonin Antagonists; Sympathetic Nervous System; Synaptic Transmission; Tropanes

Several serotonin (5-HT) receptor antagonists with varying specificities for the 5-HT receptor types, were studied with regard to their effects on blood glucose levels in mice. The non-selective antagonists, metergoline and methysergide, proved to be hyperglycemic at doses commonly used to antagonize 5-HT receptors. In contrast, ritanserin (a 5-HT2 and 5-HT1c antagonist) and MDL 72222 (a 5-HT3 antagonist) were effective only at doses which surpassed the dose range considered to be selective for their respective receptors. The results suggest that 5-HT systems play a role in maintaining glucose homeostasis and that 5-HT1 receptors may be particularly important in this function. Furthermore, the inherent hyperglycemic properties of non-selective serotonin antagonists described here, are pertinent to studies using these agents to investigate glucose metabolism.

Topics: Animals; Blood Glucose; Male; Metergoline; Methysergide; Mice; Piperidines; Receptors, Serotonin; Ritanserin; Serotonin Antagonists; Tropanes

The effect of the selective 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 on head shaking behavior induced by L-5-HTP and behavioral symptoms induced with 5-methoxy-N,N,-dimethyltryptamine (5-MeODMT) in rats was evaluated. Both drugs dose-dependently reduced L-5-HTP-induced head shaking but were at least 600 times less potent than pirenperone and ketanserin and at least 50 times less potent than methysergide. ICS 205-930 and MDL 72222 were more than 1000 times less potent than pirenperone or methysergide and 100 times less potent than ketanserin in blocking 5-MeODMT-induced forepaw treading and tremor. Since it appears that head shakes induced by L-5-HTP are mediated by 5-HT2 receptors, these data suggest that ICS 205-930 and MDL 72222 do not significantly interact with 5-HT2 receptors in the brain. Furthermore, the data suggest that ICS 205-930 and MDL 72222 lack appreciable antagonistic activity at the 5-HT receptor(s) mediating those behavioral effects induced by 5-MeODMT.

Topics: 5-Hydroxytryptophan; Animals; Behavior, Animal; Indoles; Male; Methoxydimethyltryptamines; Methysergide; Piperidines; Rats; Rats, Inbred Strains; Serotonin; Serotonin Antagonists; Tranquilizing Agents; Tropanes; Tropisetron

The effects of 5-hydroxytryptamine (5-HT) on heart rate in anaesthetized cats were analysed both in intact animals and after spinal section plus vagotomy. The intact cat responded to 5-HT (3, 10 and 30 micrograms X kg-1, i.v.) with a brief, but intense, bradycardia and a longer-lasting hypotension. Administration of MDL 72222, a selective antagonist of M-type 5-HT receptors, blocked bradycardia elicited by 5-HT without affecting that caused by stimulation of the vagus nerve. In spinal cats the same doses of 5-HT increased heart rate and blood pressure. These effects remained essentially unchanged after bilateral adrenalectomy, guanethidine, propranolol and burimamide, suggesting that 5-HT acted directly on the myocardium and blood vessels. The tachycardic responses to 5-HT in spinal cats were little affected by 0.5 mg X kg-1 doses of MDL 72222 or of the 5-HT2 receptor antagonists, ketanserin, ritanserin or cyproheptadine. In contrast, the non-selective 5-HT receptor antagonist, methysergide, which binds to both 5-HT1 and 5-HT2 recognition sites in rat brain membranes, potently antagonized the 5-HT-induced tachycardia in doses of 0.05 to 0.5 mg X kg-1. However pizotifen and mianserin, two other 5-HT2 antagonists which show poor affinity for 5-HT1 recognition sites, were also effective against the tachycardic response to 5-HT in doses of 0.5-4.5 mg X kg-1. The pressor responses to 5-HT in the spinal cat were markedly inhibited by all six 5-HT2 antagonists at a dose of 0.5 mg X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Pressure; Cats; Female; Heart Rate; Isoproterenol; Ketanserin; Male; Methysergide; Piperidines; Propranolol; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Spinal Cord; Tropanes; Vagus Nerve

In anaesthetized cats, a biphasic contraction of the urinary bladder, consisting of an initial spike followed by a longer-lasting contracture, was elicited by 5-hydroxytryptamine (5-HT) in doses of 3-30 micrograms/kg, i.a. Administration of MDL 72222 (30, 100 and 300 micrograms/kg, i.v.), which specifically antagonizes the M-type 5-HT receptors, selectively blocked the spike phase of the 5-HT response. Ketanserin (30, 100 and 300 micrograms/kg, i.v.), on the other hand, eliminated only the second phase of the 5-HT-induced bladder contraction. Injection of MDL 72222 (300 micrograms/kg) after ketanserin (300 micrograms/kg), or of 100 micrograms/kg of methysergide or cyproheptadine, or 300 micrograms/kg of ketanserin after MDL 72222 (300 micrograms/kg), led to blockade of both phases of the response to 5-HT. The contractile response to dimethylphenylpiperazinium (DMPP) remained unaffected. These results clearly show that the early and late phases of the cat urinary bladder contraction elicited by 5-HT are mediated by M and 5-HT2 receptors, respectively.

Topics: Animals; Atropine; Cats; Cyproheptadine; Dimethylphenylpiperazinium Iodide; Drug Interactions; Female; Guanethidine; Ketanserin; Male; Methysergide; Muscle Contraction; Muscle, Smooth; Piperidines; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Tropanes; Urinary Bladder

The effects of 5-hydroxytryptamine (5-HT) on spontaneous and electrically-evoked release of [3H]-acetylcholine (ACh) from guinea-pig myenteric plexus preparations preincubated with [3H]-choline have been investigated in the absence of cholinesterase inhibitors. 5-HT caused a transient increase in spontaneous release and an inhibition of the electrically-evoked release of [3H]-ACh. The 5-HT-induced contractions of the longitudinal muscle were clearly related to the increase in spontaneous release. The inhibitory effect was not due to activation of alpha-adrenoceptors since it was also observed in the presence of tolazoline and on strips from reserpine-pretreated guinea-pigs. After desensitization of the excitatory 5-HT receptors with 5-HT or metoclopramide the effects of 5-HT on spontaneous [3H]-ACh release were largely reduced. A variety of established antagonists at neuronal 5-HT receptors (i.e. metitepine 0.1-1 microM; methysergide 1 microM; ketanserin 0.1-1 microM; MDL 72222 0.1 microM; tropacocaine 1 microM) failed to block the excitation. The inhibition by 5-HT of the electrically evoked [3H]-ACh release was competitively antagonized by metitepine (pA2 7.6) and methysergide (pA2 7.0) but not by ketanserin. Tachyphylaxis to the inhibitory action of 5-HT did not occur. The results suggest that the excitatory 5-HT receptor ('M'-receptor) differs in its pharmacological properties from other neuronal 5-HT receptors. The presynaptically located inhibitory receptor may roughly correspond to the 5-HT1 receptor subtype but probably differs from the 5-HT autoreceptor.

Topics: Acetylcholine; Animals; Binding, Competitive; Cocaine; Electric Stimulation; Female; Guinea Pigs; Ketanserin; Male; Methiothepin; Methysergide; Metoclopramide; Muscle Contraction; Myenteric Plexus; Piperidines; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Tropanes

The effects of intracarotid (i.c.) injections of 5-hydroxytryptamine (5-HT; 1-50 micrograms) on carotid chemoreceptor activity recorded from the carotid sinus nerve have been studied in anaesthetized cats. Three separate components in the complex response of the chemoreceptors to injected 5-HT were identified. Firstly, a transient burst of activity was obtained during the injection period in 56% of the recordings. Secondly, in all the recordings a period of chemodepression commenced a few seconds after completing the injection and was usually dose-related. Thirdly, a delayed longer-lasting chemoexcitation occurred in many experiments, concomitant with a fall in systemic blood pressure. The neuronal 5-HT receptor antagonist MDL 72222 (10-100 micrograms kg-1, i.c.) virtually abolished the transient chemoexcitation evoked during 5-HT injections and also significantly increased the mean ID50 for 5-HT-induced chemodepression; in 37% of recordings 5-HT caused a dose-related chemoexcitation after the high dose of MDL 72222. Neither the delayed chemoexcitation nor the hypotension caused by 5-HT were much affected by the antagonist. MDL 72222 itself had a biphasic effect on chemosensory discharge, causing depression followed by a delayed excitation. The 5-HT2-receptor antagonist ketanserin (100 micrograms kg-1, i.c.) had no appreciable effect on the transient chemoexcitation evoked during 5-HT injections and caused a slight but significant increase in the mean ID50 for 5-HT-induced chemodepression. The delayed chemoexcitation and accompanying hypotension associated with 5-HT were both substantially reduced or abolished by the antagonist. Ketanserin itself caused a short-lasting period of chemoexcitation. All the effects of injected 5-HT on chemosensory discharge could be abolished by the combination of MDL 72222 and ketanserin (100 micrograms kg-1, i.c.). Neither MDL 72222 nor ketanserin had any significant effect upon the response of the carotid chemoreceptors to hypoxia. The rate at which discharge increased, and also the steady-state discharge before and during hypoxia, were unaffected by the antagonists, alone or in combination. At least two types of 5-HT receptor appeared to be involved in the response of carotid body chemoreceptors to 5-HT. Transient excitation and chemodepression were mediated via MDL 72222-sensitive (peripheral neuronal) receptors whereas the delayed chemoexcitation and associated hypotension involved a ketanserin-sensitive, presumably 5-H

Topics: Action Potentials; Animals; Carotid Body; Cats; Chemoreceptor Cells; Domperidone; Dopamine; Electrophysiology; Female; Hypoxia; Ketanserin; Male; Piperidines; Serotonin; Serotonin Antagonists; Tropanes