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 3_ Federal Rs_er / V0L 51. Non 198 / TUesday, October 14, 198@ / Ru|e8 and Rsgu]ations
 __ n
 35. Studies conducted by Dro Harris at lethal than mescaline but leas lethdd test dro8 and the standard dry 8 are
 the Medical College ef Virginia than MDA, assumed to have similar abuse potentt_
 compared the locomotor activity Ln mice 42. Intraperitoneal LD_'s for _A if the reinforcing propertles and adverse
 using d_amphetamine and IMDMA. Dro and MDMA were determined in mice by effects of the standard and test drugs
 Herds fouRd that MDMA produces Dr. Davis. The LD_'s of MDMA and are similaro
 slightly _ess central nervous system MDA were substantially the _ame w_th 52. In drug discrLmination paradigms
 stimulation than amphetamine at peak the Ll_ for MDA equalling 90_0 rnl_./kg, complete genereliaation indicates that
 activity which is 1½ hour_ after and the LD_ for MDMA equa_llng I06.5 the teat compound is similar enough fat
 administration. However, at 5-15 mg./kgo Dro Hardraan faired the LD_ of the animal to recognize it as the trainhn_
 minutes and 2-._ hours after MDA to be 92 mg./kg. Davis also found drug by responding on the appropriate
 administration, the ma×imu_a that both MDA and MDMA _howed the drug lever at least 80% of the time. No
 stimulatlng effect of MDMA is _mphetamin_like property of incroaaed generalization indicates that the _est
 substantlally greater than that produced lethality under aggregated housln_ compound is unlike the training
 by d-amphetamlne, conditions compared to isolated hcmsing compound so that a low number of
 i 36. MDA and MDMA produce _i_]ar conditionso responses will be made on the drug
 i centrally mediated analgeslc effects in 45. In the study conducted by L_to_ lever° Partial generalization indicates
 i mice as determined by the hotoplats tat, L_borato_es the oral LD_ fop MDMA IR that there may be pharmacological
 i the Sail-flick test and the stretch teal rats was estimated to ba approximately effects common to both test and _rainir_
 The fail-flick test and hot-plate test _S m_o/l_ No oral value was reported drug. but that some doses of the _ea_ and
 showed that MDMA produces a_ for MDA0 but based on the data from training drug _re similar and that_ at the
 ...... increased analgesic effect over that _n_ox Laboratories, Dr. Hardma_ tested doeas, another type of
 produced by MDA. _timated it to b, approximately It_ pharmacological effect may
 37. MDA and MDMA both produce an mg./_o predomineteo
 increase in body temperature when _o MDMA. _)A, amphet_mlr_e and
 administered to rabbit_ at similar methamphetamine produce na_xotoxic _3. MDMA shares discriminative
 potencies. Hyperthermia _n rabbits is effects when administered to shiraz|p, stimulus properties in common with
 reported to be a measure of central MDMA and MDA are neurotoxlc in rats amphetamine and MDA in drug
 nervous system activity. Dr. Shulgin at doses which are very low compared discrimination studies in rata.
 notes that there is a reasonably good to the neuroto×ic doses of amphetamine 5._o Xn a dr_s discrimination test
 parallel between the hyper_srraia and methamphetaminao described by Dr. Glennon_ rats trained
 response in rabbits and some of the 45. MDtvtA and MDA both produce to recognize amphetamine also
 effects of LSD, and that these parallel lor_g term reduction in serotcnin levels recogni:zed MDA and MDMA. M_)MA
 quite closely the psychopharmacological and serotonin up_ke sites in the r_ t was slightly more potent th_ Iv_2A in
 potency i_ humans. He believes that it i_ brain. Thane neurochemics| deplatlon_ being recognized as amphetamine. Oth_
 probably the best animal test at present are due to the des_'uoflon of _erotoni_ compounds which generalized to the
 fo_ estimating psychotoraim_tlc potency, nerve terminals a_ determined by visual amphetamine stimulus included
 38. Both MDA and MDMA are potent staining tschnlques, methamphet_mlne, cocaine and pars®
 ra_eaaerrs of serotonin or _ 46. la htunan_, serotonin nerve mathoxyamphetamineo
 hydro×ytryptsmine, a naurotransmitter terrainals _re believed to play a ma ior 55. Rats trained to recognize MDA
 which has • widely accepted role in the role hn mood, emotion, pain perceptlo_ recognised MDMA in drug
 activity of hallucinogens. _leep _a_d affect the regulation of discrimination studies conducted by Dr.
 3_. In mice, dogs and monkeys, MDA aggressive and sexual behavior. Glsmno_
 and MDNLA produce the same spect_ ,_7_ Although single Iniectlon_ of Sac _A completaiy generalized (_
 of pharmacological effects when _MA may be slightly less neurotuxic correct response] in rats trained to
 observed during toxicity studies. These than MDA_ MDMA, used c.hroni_lly, recognize 4-methyl-_
 effects include hyperactivity_ appears to be mote neuroto_ic thar,_ dimetho×yamphetamina (DAM], a
 excitability, emesis, apprehension or MDAo substance with known hallucinogenic
 f_ght, aggressive behavior, bizarre body _8. The neumto×Iclty of amphetamine prol:_rties, but only within a very
 attitudes, apparent hallucinations, and methsmph_t_mine haa been narrow dosage range.
 dyspnea and hyperpnea. Motor activity deter_PJLned in rats, _uinea pigs and
 effects include conwalsions, muaoulsP monkeyao 5?. MDMA showed partial
 rigidity and tremor_ and the autonomic 48_ MDMA and MDA may produ_ the _ener_li_ation (5_ correct response} i_
 activity includes mydriaeis, pilo_rectlon_ same natu_oto_dc _ffecte to serotnne_tc rata trained to recognize DaM, at a
 salivation and vascu_a_ flushing. These nerves in huma_eo specific dose.
 effects are part of what is described aa ,50. Dr_ discrimination _tudi_ i_ 58. A standard abuse liability test for
 the classical pharmacological response animal_ allow one to determine if • _esessi_g the reinforcing properties of s
 of the do 8 to intravenous mescaline, pa_tcular dose of a test substance drn8 is the substitution procedurso It is
 40. The lethality of a compouRd is producea effects which are recogni_:ed the most common and reliable method
 reported as a_ LD_, which is the dose of as khe same a_ those produced by a for determining whether a chug will be
 drug which will kill 50_ of the a_.mal_ particular dose of another substance. It salf-administer_d. Ln thla procedure,
 frosted with that dose+ is believed that the effects recreated new drugs are tasted to determine
 _1. The _'s for mescalL_e, MDA by the a_all_ in _ese s_udies are whether or not they will maintain the
 and MDMA were determined by _ntral nervous system effects end re_pon_n_ of animals _ained to press
 intravenous or Intraperitone_ hence thla paradi_n is very useful in lever for intravenous delivery of a
 administration in five species of cbaracterizin_ centrally acting known drug reinforcer.
 animals. MDMA had LD_'s between _ compounds. _9o _u teats conducted with rhesus
 and S times less than those of mssc_llne _. If a test drug in animal drug monkeys and baboons trained to self+
 and between los _d 3 times more than discr_mlna_ion studies elicits _imilaP ad.mlnlater cocaine, the monkeys and
 MDA_ This means that MDMA is more responses to a standard dru_, both the baboons continued to self-admlnister

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