Brain serotonin receptors as a target for the putative anxiolytic TVX Q 7821

Ipsapirone (TVX Q 7821, 2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-1,2-benzisothiazol-3- (2H)one-1, 1-dioxidehydrochloride), a new anxiolytic drug in respect of the evaluation of its effect on central 5-hydroxytryptamine (5-HT), noradrenaline and dopamine functions was studied. It was found that ipsapirone inhibits induced by 8-OH-DPAT and 5-methoxydimethyltryptamine (agonists of 5-HT1A receptors) behavioural effects (flat body posture and forepaw treading) in normal and reserpinized rats. Ipsapirone partly inhibited in rats but not in mice the 8-OH-DPAT-induced hypothermia. Ipsapirone, administered at high doses, decreased the body temperature in rats and mice, inhibited the 5-hydroxytryptophan-induced head twitches in mice and the tryptamine-induced convulsions and tremor in rats. In the hind limb flexor reflex preparation of the spinal rat only high doses of the drug inhibited stimulation induced by quipazine, m-chlorphenylpiperazine, 8-OH-DPAT and St 587 (an agonist of alpha 1-adrenoceptors). Ipsapirone did not block the fenfluramine- and m-chlorphenylpiperazine-induced hyperthermia in rats at an ambient temperature of 28 degrees C. The drug did not affect clonidine-induced sedation and inconsiderably attenuated clonidine-induced hypothermia in mice. It attenuated the d-amphetamine-induced locomotor hyperactivity in mice and rats but, given alone, decreased the locomotor activity. The obtained results indicate that ipsapirone exhibits 5-HT1A antagonistic effect, and only at high doses it can also produce an inhibitory effect on 5-HT2 and the alpha 1-adrenergic function.

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“…This finding corroborates some earlier data about the actual lack of binding to dopamine receptors Traber et al, 1984).…”

Section: Dopamine Functionsupporting

confidence: 92%

Central action of ipsapirone, a new anxiolytic drug, on serotoninergic, noradrenergic and dopaminergic functions

Chojnacka-Wójcik

Tatarczyńska

et al. 1987

J. Neural Transmission

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“…5-HT~ antagonists: ipsapirone, spiperone, pindolol, cyanopindolol, compound 21-009, mesulergine (Tricklebank et al, 1985;Hoyer et al, 1985 a;Traber et al, 1984;Engel et al, 1986); 5-HT2 antagonists: cyproheptadine, mianserin, methysergide (Peroutka, 1986;Engel et al, 1986); 5-HT3 antagonists: ICS205930, metoclopramide (Fozard et al, 1979;Richardson and Engel, 1986); other drugs: pimozide (a neuroleptic), idazoxan (an cz2-adrenoceptor antagonist), atropine (cholinolytic), atenolol (13-adrenoceptor antagonist).…”

Section: Introductionmentioning

confidence: 99%

Hypothermia induced by m-trifluoromethylphenylpiperazine or m-chlorophenylpiperazine: an effect mediated by 5-HT1B receptors?

Chojnacka-Wójcik

Kłodzińska

et al. 1988

J. Neural Transmission

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In the present study we examined the effect of different drugs on the m-trifluoromethylphenylpiperazine (TFMPP)- and m-chlorophenylpiperazine (m-CPP)-induced hypothermia in mice. Both the hypothermias studied are blocked or reversed by pindolol, cyanopindolol and compound 21-009, but not by atenolol. Neither hypothermia is antagonized by 5-HT1A antagonists (ipsapirone, spiperone), a 5-HT1C antagonist (mesulergine), 5-HT2 antagonists (cyproheptadine, mianserin, methysergide), 5-HT3 antagonists (ICS 205930, metoclopramide). The examined hypothermias are not antagonized by other antihypothermic agents (pimozide, idazoxan, atropine). The 8-OH-DPAT-induced hypothermia is not affected by cyanopindolol or compound 21009. The obtained results indicate that the TFMPP- and m-CPP-induced hypothermias in mice are mediated by 5-HT1B. These hypothermias may be a good screening test for evaluation of the 5-HT1B-agonistic and 5-HT1B-antagonistic activity.

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“…In fact, 3e and ipsapirone show similar affinities for 5-HT 1A receptors (K i = 1.25 nM and 2 nM [18] , respectively), both these compounds induce LLR in rats, the maximum effect (ca. 80%) being observed after 20 mg/kg of 3e and after 4.6 mg/kg of ipsapirone [10] .…”

Section: -----------------------------mentioning

confidence: 95%

Novel 1,4-Benzoxazin-3(4H)-one, 1,2-Benzoxazolin-3-one and 1,3-Benzoxazolin-2,4-dione Arylpiperazine Derivatives with Different 5-HT1A and Antagonistic 5-HT2A Activities

Mokrosz¹,

Kowalski

Kowalska

et al. 1999

Arch. Pharm. Pharm. Med. Chem.

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Brain serotonin receptors as a target for the putative anxiolytic TVX Q 7821

Cited by 137 publications

References 5 publications

Central action of ipsapirone, a new anxiolytic drug, on serotoninergic, noradrenergic and dopaminergic functions

Central action of ipsapirone, a new anxiolytic drug, on serotoninergic, noradrenergic and dopaminergic functions

Hypothermia induced by m-trifluoromethylphenylpiperazine or m-chlorophenylpiperazine: an effect mediated by 5-HT1B receptors?

Novel 1,4-Benzoxazin-3(4H)-one, 1,2-Benzoxazolin-3-one and 1,3-Benzoxazolin-2,4-dione Arylpiperazine Derivatives with Different 5-HT1A and Antagonistic 5-HT2A Activities

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